effect of respiratory and other virus infections on ige immunoregulation

Effect of respiratory and other virus infections on IgE immunoregutation

Oscar L. Frick, M.D., Ph.D. San Francisco, Calif.

An association between respiratory infections and sub- sequent development of asthma was noted by Hippocrates.’ He also recognized the hereditary nature of asthma, which was confirmed formally first by Cooke and VanderVeer’ and later by others. Asthma was classified into extrinsic (allergic) and intrinsic (infectious) forms by Rackemand; this has been a useful working hypothesis, although we now recognize the inflammatory nature of chronic asthma. Cli- nicians have known for years that respiratory tract infections often precede asthma attacks. In young children (younger than 5 years) before and during asthma attacks, respiratory syncytial virus and parainfluenza infections were docu- mented by direct isolation or rising antibody titers in 41% of subjects in the classic study by McIntosh et al4 In older children and adults, Minor et a1.5 found that rhinoviruses and influenza were commonly implicated in asthmatic ep- isodes.

VIRAL INFECTION ASSOCIATED WITH ONSET OF ALLERGY

A prospective study of 24 infants who were born into families with two allergic parents was started in 1975 to investigate whether external factors beyond genetics influ- enced the onset of atopy.6 At 3-month intervals from birth, these infants were examined for clinical signs of allergy. Several immunologic tests were done for serum immuno- globulins IgE, IgG, IgM, and IgA and for RAST, LHR, and lymphoproliferation with a panel of six common allergens. Results were compared with those in a group of 28 well babies from nonatopic families in whom allergy had been ruled out by history. In the allergy-prone children, after 2 years, a score of 88 symptoms and signs of allergy from a possible score of 120 (five symptoms times 24 subjects), or 73% positive, was observed. This was significantly greater at p < 0.01 when compared with 21 of 140 signs and symptoms in the 28 control children (15% positive).

The immunologic test results also showed a significantly greater percentage of positive immunologic test results for allergy for all three tests (61%) compared with nonallergic controls at lo%, p < 0.01. In children with hay fever tested for grass pollen, 80% had reactions. Most striking was the timing of the onset of positive clinical and immunologic test

From the Department of Pediatrics, University of California-San Francisco, San Francisco, Calif.

Supported by research grants from the U.S. Public Health Service, National Institute of Allergy and Infectious Diseases (3P50 AI1 1010, ROI-15233). and by A.G. Spanos Family Allergy Re- search Fund.

Reprint requests: Oscar L. Frick, M.D., Ph.D., Department of Pediatrics, University of California, San Francisco. CA 94143.

Abbreviations used CFA: Complete Freund’s adjuvant

ConA: Concanavalin A CPI: Canine parainfluenza virus vaccine

DNP: 2,4-Dinitrophenyl EFA: Enhancing factor of allergy

Fc,R+: IgE Fc receptors LHR: Leukocyte histamine release

Lyt 1 +: Mouse T-lymphocyte 1 + PCA: Passive cutaneous anaphylaxis

Poly I : C: Polyinosine, polycytosine acid PWM: Pokeweed mitcgen RAST: Radioallergosorhent test

RSV: Respiratory syncytial virus SFA: Suppressive factor of allergy

I

J

results immediately after respiratory tract infections, such as in patient 1 (Fig. 1). This patient had a sharp rise in total IgE from <5 U/ml to 50 U/ml within 3 months after three upper respiratory tract infections; high RAST and LHR with cow’s milk, house dust, and cat dander also developed. He also had a fourfold rise in complement-fixing antibodies to parainfluenza 3 during this same 3-month interval. Such rising patterns of IgE, RAST, LHR, and lymphoproliferation with allergens occurred in 21 of 24 children, but failed to occur in three. In 15 of 24, rising antibody titers to parainfluenza and RSV occurred in the 3 months spanning the start of allergic symptoms and immunologic test changes; six of 24 already had high titers, whereas in three there were few symptoms or changes in viral antibody titers. These results suggested a temporal association between viral respiratory tract infections and the onset of allergy, but there was no actual proof. Bahna et al.’ had shown sharp rises in total IgE during infectious mononucleosis, and postin- fection suppression of IgE. Perelmutter et al8 also found high IgE levels in several patients with acute viral infections, and lower IgE levels during convalescence. The findings suggested an IgE immunoregulatory role for certain viral infections, especially in atopy-prone children.

CANINE MODEL OF IWHXTKW OF ALtlERoY WlTH VIRAL VACCINATION

The dog is the only animal, other than humans, that fre- quently becomes atopically sensitive to pollens, as reported by Wittich9 and by Patterson.‘” At the University of Cali- fornia, Davis, 220 hunting dogs were screened by intra- dermal skin tests for reactions to a 1O-5 dilution of mixed grass and weed pollen extracts.” Seven dogs (two males and five females) were bred. Pups were injected simulta-

1013

1014 Frick J. ALLERGY CLIN. IMMUNOL.

NOVEMBER 1986

VIRUS CF TITERS

8163264

ADENO RSV

PARAINF 1 2 3

. CMV MP

8 163264 0

#

be-- CAT 0 EE- H.D. MITE

a@--- COW MILK ora- soy

E/C 2*o (nRAST)

(0LJ-o

9 SKIN

N

60

HR%

(0) 20

I NOSE Cl CHEST wheeze

stir

CUk.+hddl.3 AGE -MONTHS

FIG. 1. Clinical and immunologic assessment of patient 1. E/C, experimental/control ratio for RAST-/gE, lymphoproliferation (LTT), and percentage of histamine release from leukocytes (basophils) (HR?h). Months listed on abscissa (6 February; My, May; Au, August; N, November). Feeding represented by N (nursing) and SOY (soybean formula). Complement-fixing virus antibodies shown for adenovirus (ADENO), respiratory syncytial virus (RSV), parainfluenza (PARAINF

1, 2, 3). cytomegalovirus (CMV), and Mycoplasma pneumonia iMPI. Sx, symptoms; UR/, upper respiratory tract infection.

neously with live attenuated distemper-hepatitis virus vaccine at 4, 8, and 12 weeks of age, followed in 2 and 9 days by 10 kg grass and ragweed pollen extract in 2 mg alum in each axilla, respectively. Littermate controls received only the pollen extracts, and no viral vaccine until 2 weeks after the pollen. Consistently, the vaccinated pups produced more IgE antibodies to both pollens than did their unvac- cinated littermates.” In a longitudinal 2-year study of a different litter, IgE to both pollens, as measured by canine RAST and PCA, rose initially, reached a plateau, and rose precipitously after the first- and second-year annual distemper vaccine booster immunization. In about 10% of the pups, facial dermatitis developed during the grass pollen season (eczema is the main allergic manifestation in dogs).

To simulate the natural events more closely, pups at 3, 7;and 11 weeks were given IO-fold concentrated attenuated canine parainfluenza virus vaccine intranasally, followed by four l-hour inhalation exposures in a plastic chamber to 2% aerosolized pollen extracts; littermates received only the pollen extract inhalations. The vaccinated pups developed more IgE antibodies to both pollens than did their littermate controls.

“ALLERGIC BREAKTHROUGH” MECHANiSM

Immunoregulation of IgE antibodies appears to be in part independent of IgM, IgG, and IgA production. Models of IgE antibody production have been studied extensively in different strains of mice,‘* parasite-infected rats,” and most recently in lymphocyte subset co-cultures in animals and in humans.“. I5 The IgE antibody formation by B cells that differentiate into IgE-producing plasma cells is regulated by T helper and T suppressor lymphocytes.‘6

These studies in atopy-prone children and inbred dogs indicated that myxovirus infections appeared to affect IgE immunoregulation, and possibly the development of atopy. Katz” proposed an “allergic breakthrough theory” on the basis of his studies in inbred mice. In the simplest terms, IgE pre-B-lymphocytes differentiate and proliferate into ma- ture B cells and plasma cells to make IgE antibodies. These B cells receive signals from regulatory T-lymphocytes that direct their differentiation. If antigen is processed by macrophages, a signal is passed to T inducer cells, which initiate B cells to differentiate and proliferate. If antigen stimulates T suppressor lymphocytes directly, the signal is for B cells not to differentiate. A change in the balance of signals from

VOLUME 78 NUMBER 5. PART 2

Effect of infections on IgE immunoregulation 1015

Disturbance of Heightened damping mechanism damping mechanism

“Damping” mechanism

Sensitization Sensitization Reversal of allergic breakthrou&

FIG. 2. Possible pathogenesis of “allergic breakthrough.” (From Katz DH. J lmmunol 1979;122:2191.)

T regulatory cells determines whether B cells will differentiate and produce IgE antibodies.

It was thought that SJL mice were genetically deficient in IgE-responsive cells; they were “IgE nonresponders.“‘” Chiorazzi et al.19 showed that SJL mice given low-dose irradiation, cyclophosphamide, or antilymphocyte serum 10 days before antigen subsequently had good IgE antibody responses. The addition of normal spleen cells from syn- geneic untreated SJL mice abrogated the IgE response caused by infusion of fresh splenic T suppressor cells. KatzI proposed that IgE suppressor T cells exerted a “normal damping effect” on IgE B-cells that keep most individuals in the “nonatopic state.” However, stimuli such as irradiation and cyclophosphamide, which depress T suppressor cells preferentially, allow escape of T inducer and B cells to produce IgE antibodies. The individual then becomes atopic; thus the term “allergic breakthrough.” Stimulation of T suppressor cells, as in immunotherapy, would reestab- lish the. “damping mechanism” and return the subject to the nonatopic state (Fig. 2).

It is suggested that myxovirus infections act to. upset the balance among these regulatory T-lymphocytes to initiate IgE antibody production to antigens at hand in the environ- ment and diet to which the individual is genetically capable of reacting, as in pollen-atopic dogs.

To test this theory, a human model was used where there were available monoclonal antibody markers for T-lymphocyte subsets. *’ One booster immunization of live attenuated measles virus vaccine was given to eight normal adults and nine atopic adults with hay fever or asthma. All had a history of measles during childhood. Blood samples for determination of numbers, percentages, and ratios of T cell subsets (inducer OKT4/suppressor OKT8) were taken twice before and daily for 5 days and at 3- to Cday intervals after the measles vaccine booster. Both groups had sharp ele- vations in both number and percentage of T inducer cells (OKT4) within 48 hours, with a return to prebooster levels by 4 days in the nonatopic individuals. In atopic subjects it took longer, 7 to 14 days, for levels to return to baseline. It is interesting that atopic subjects had about 10% more T inducer cells and 5% less T suppressor cells than nonatopic subjects at baseline. T suppressor cells (OKT8) showed little change; slight decreases in both groups were not statistically significant. Similarly, ratios of OKT4/OKT8 cells rose

sharply in both groups, with a peak in 48 hours in the nonatopic subjects and return to baseline in 4 days. In the atopic subjects this ratio peaked in 72 hours, with a gradual return to baseline (Fig. 3). The serum total IgE level rose in atopic subjects who had a high initial IgE level at the same time; low IgE atopic and nonatopic subjects showed no change in level. The overall changes in IgE levels, however, were not statistically significant. These studies indicate that live measles virus vaccine has an immediate, but tran- sient, effect on T regulatory cell balance and probably IgE production. This disturbed balance persisted longer in atopic than in nonatopic subjects.

IgE lMMUfUOREGULATORY FACTORS

Antigen in CFA generally induces high levels of IgG and IgM antibodies2’ However, Katz et al.*’ observed that mice given antigen in CFA failed to produce IgE antibodies; in fact, CFA appeared to suppress IgE production. However, antigen in alum enhanced IgE responses. Serum from CFA- treated mice inhibited IgE production when injected into normal mice. From such sera, Katz isolated a “suppressive factor of allergy,” which suppressed IgE antibody responses in mice to many antigen3 nonspecifically. Subsequently an “enhancing factor of allergy” was isolate both SEA and EFA acted only on the IgE system, with no regulatory effect on IgM, IgG, or IgA antibodies. A lectin affmity column with ConA failed to bind SFA, but bound EFA, which could then be eluted with excess mannose. Human SFA has been found in supematants of PWM-stimulated cuttured human lymphocytes, which prevents or abrogates IgE production in mice.

Soon after the discovery and characterization of IgE jointly by Ishizaka et al.23 and Johansson et al.,% the latter investigators found that Ascuris-infected Ethiopian children had extremely high serum IgE levelsz5 OrP observed that rats infected with the rat hookworm Nippostrongylus brasiliensis had a “nonspecific potentiation” of IgE beyond just antiparasite antibodies. Suemura and Ishiz&? found that within 10 days after N. hsiliensis infection in rats, mesenteric lymph node T cells in culture produced an IgE potentiating factor. Yodoi et al.” next found that a small amount of IgE was necessary as a primer, and when mesenteric lymph node T cells were incubated with 10 t.i,g ConA and IgE, such cells expressed surface Fc.R+ and produced

1016 Frick J. ALLERGY CLIN. IMMUNOL.

NOVEMBER 1966

3.0 0

MEAN

TH’TQ

RATIO

ATOPICS (8) x-z

CONTROLS (9) o--o

// II * I

Pm Pm ~ 1 2 3 4 5 6 7 10 14 22

RAV DAYS

0.w

P NS - YS NS <.Ol <.os NS

FIG. 3. Ratio of T inducer/T suppressor lymphocytes after rubeola attenuated vaccine (MV) in eight atopic and nine nonatopic human subjects.

IgE-potentiating factor in the supernatant. Following Katz’s lead with lectin-affinity columns, Yodoi et alZ9 found that the IgE potentiating factor in supematants was removed with a lentil lectin column, whereas IgE suppressive factor remained in the effluent. IgE potentiating factor could then be eluted from the column with o-methyl mannoside. Ishizaka called both factors IgE binding factors, but with either IgE potentiating or suppressive effects.

Because of the apparent importance of sugars, especially mannose, in determining the regulatory activity of IgE binding factors, Yodoi et alM cultured rat mesenteric lymph node T-cells in the presence of 10 Fg IgE and ConA to produce IgE potentiating factor; they treated such cells with tunicamycin, which blocks glycosylation, and were sur- prised when IgE suppressive factor appeared in the supernatant. Furthermore, when such cells treated with 10 p,g IgE and ConA were also treated with 5 pg dexamethasone, which induces lipomodulin and inhibits phosphorylase, again IgE suppressive factor occurred in the supematant. This suggested a modulatory action of sugars and cortico- steroids on IgE antibody formation.

When antigen-primed T-cells were restimulated with antigen, T inducer cells formed lymphokines, such as inducer of IgE binding factors, and expressed surface Fc,R+ . Other or perhaps the same antigen-stimulated T cells produced glycosylation regulation factors that determined the nature of the IgE binding factors that were produced. T inducer

cells produced a glycosylation enhancing factor that induced the Fc,R+ inducer cells to produce IgE potentiation factor. Other T cells produced a glycosylation inhibition factor, which caused Fc.R+T cells to form IgE suppressive factor.“’ The balance of the production of these factors determined whether IgE antibody to that antigen was produced.

INFECTIONS AND INTERFERON ASSOCIATED WITH IgE lMMUNOREGULATORY FACTORS

Killed Bordetella pertussis organisms injected into mice and rats are known to make the animals susceptible to anaphylaxis. 32 Both Morse et a1.j3 and Munoz and BergmarP had isolated from B. pertmis a lymphocyte promotion factor, or “pertussigen,” which induced histamine sensitization and had an IgE adjuvant effect. Hirashima et a1.‘5 and Ishizaka36 wondered if this could be IgE potentiation factor. Rats were given 10”’ B. pertussis organisms intraperitone- ally. Within 5 to 7 days, T cells in cultures expressed Fc,R+ and produced IgE potentiating factor, which also was present in the sera. They concluded that IgE potentiating factor was the basis for the adjuvant effect of B. pertussis on the IgE response.

Effects of other infections on IgE production were suggested by Yodoi et al.,” who found that when normal mouse spleen cells were co-cultured with measles virus-infected HeLa cells, interferon formation was induced in supematants. When this supematant was incubated with rat mes-

VOLUME 78 NUMBER 5, PART 2

enteric lymph node T cells, IgE suppressive factor was formed. However, treatment of the supematant with rabbit anti-mouse a-interferon removed the IgE suppressive factor; this suggested that interferon was an inducer of IgE suppressive factor.

Polyinosinic, polycytosinic acid induced cells to form interferon in rodents. Culture filtrates of rat spleen cells stimulated with poly 1:C were added to normal rat mesenteric lymph node cells and incubated with either 1 or 10 pg ConA for 2 or 3 days, respectively.” With 1 yg ConA, poly I : C induced mesenteric lymph node cells to form IgE suppressive factor; with 10 pg ConA, poly 1: C induced IgE potentiating factor formation.

Similar effects of interferon on IgE regulation occurred in a murine model. First, 10 pg mouse IgE cultured with normal mouse spleen cells with Lyt 1 + T cells induced Fc,R+ and production of IgE binding factors. Poly I: C caused splenic macrophages to produce IX- or p-interferon, which induced the normal mouse spleen Lyt 1’ cells to produce IgE suppressive factor; this induction of IgE suppressive factor was prevented by absorbing the supematant with sheep anti-P-interferon serum, which removed the p-interferon. Purified mouse p-interferon induced BALB/c mouse spleen cells with Lyt 1 + T cells to express Fc.R+ and produce IgE binding factors. The IgE potentiating factor bound to ConA and lentil lectin affinity columns, and IgE suppressive factor bound to affinity columns with peanut agglutinin?

Different inbred mouse strains had variable, apparently genetically determined abilities to produce IgE binding factors.” With 10 pg mouse IgE in culture, BALB/c and C57BL/6 mouse spleen cells made both IgE potentiating and suppressive factors in about equal amounts. However, high IgE responder BDF, mouse spleen cells made 75% IgE potentiating factor and only 25% IgE suppressive factor; these might correspond to atopic human beings. On the contrary, the IgE nonresponder SJL mice made only about 10% IgE potentiating factor and 90% IgE suppressive factor; these might correspond to atopy-refractory individuals.

In vivo experiments showed that C57BLi6 mice given live Sendai viruses (parainfluenza 1 virus) intranasally and immunized the next day with 2 kg DNP-keyhole limpet hemocyanin promptly made a brisk IgE anti-DNP PCA response that peaked on the third day. Similarly, but more slowly, nonresponder SJL mice given Sendai viruses intranasally and immunized with 2 pg DNP-keyhole limpet hemocyanin made IgE anti-DNP antibody with a peak at day 10, which indicated that the virus had induced even an IgE nonresponder strain to make more IgE potentiation factor and manifest an IgE response.4”

Returning to the human model, Saryan et al.“’ found that peripheral blood mononuclear cells of atopic individuais spontaneously produced IgE de novo in culture from 180 to 1600 pglml, but that mononuclear cells from nonatopic persons failed to make IgE. However, nonatopic mononuclear cells stimulated with PWM or Epstein-Barr virus produced no IgE, but did make 2400 to 8000 pg/ml IgG. When normal B cells were incubated in cultures with supernatants from norma T cells, no IgE synthesis occurred. However,

Effect of infections on IgE immunoregulation 1017

with T cell supematants from patients with hyper-IgE syn- drome, atopic dermatitis, or acute graft-versus-host reactions, considerable de novo IgE synthesis occurred at 300 to 5900 pg IgEI IO6 cells.

If interferon induced by viruses does play a role, what actually happens remains unknown. Viruses act on the cells and ultimately IgE is produced. Fitzpatrick and Stingfellow4* showed that viral infections and interferon cause rises in prostaglandins in macrophages. A preliminary experiment with T cells from an atopic person co-cultured with nonatopic and atopic B cells showed increased IgE and PGE, in the supematants from atopic B cells, especially when cultured in the presence of human p-interferon (Frick OL, Saxon A, unpublished study). It is conceivable that prostaglandins affect cyclic nucleotides that modulate IgE production, but this is still speculative.

OTHER EFFECTS OF VIRUSES IN ALLERGY

Finally, viruses may have other effects in allergic individuals. Influenza viruses denude the bronchial mucosa, exposing irritant cough receptors that cause nonspecific bronchial hyperreactivity.4’ There may be increased absorp- tion of allergens across a denuded mucosa. Busse@ showed increased P-adrenergic blockade in granulocytes induced by influenza viruses. Ida et al.45 found augmented histamine release from pollen-sensitized basophils by viruses and interferon. Welliver et aI.* demonstrated specific IgE antibodies to RSV and parainfluenzae in nasal secretions of wheezy infants.

In summary, myxoviruses, and possibly others, appear to have effects on the immunoregulatory cells involved in IgE antibody production, as shown in atopic children and dogs. Myxoviruses are strong inducers of interferon, which may be the mechanism whereby such immunoregulatory effects are mediated.

REFERENCES

I.

2.

3. 4.

5.

6.

Hippocrates. The genuine works of Hippocrates, translated by F. Adam. Baltimore: 1939, Williams & Wilkins. Cooke RA, VanderVeer A Jr. Human sensitization. J Immunol 1916;1:201. Rackemann FM. Intrinsic asthma. J Allergy 194O;ll: 147. McIntosh K, Ellis EF, Hoffman LS, Lybass TG, Eller JJ, Fulginiti VA. The association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children. J Pediatr 1973;82:578. Minor TE, Dick EC, DeMeo AN, Ouellette JJ, Cohen M, Reed CE. Viruses as precipitants of asthmatic attacks in children. J Am Med Assoc 1974;227:292. Frick OL, German DF, Mills J. Development of allergy in children: association with virus infection. J ALLERGY CLIN IM- MUNOL 1979$X228. Bahna SL, Horowitz C, Fiala M, Heiner DC. IgE response in heterophil-positive infectious mononucleosis. J ALLERGY CLIN IMMUNOL 1978;62: 167. Perelmutter L, Phipps P, Potvin L. Viral infections and IgE levels. Ann Allergy 1978;41:158. Wittich F. Spontaneous allergy (atopy) in the lower animal. Seasonal hayfever in a dog. J Allergy 1941;12:247.

1018 Frick J. ALLERGY CLIN. IMMUNOL. NOVEMBER 1996

10. Patterson R. Investigations of spontaneous hypersensitivity in the dog. J Allergy 1960;31:351.

11. Frick OL, Brooks DL. Immunoglobulin E antibodies to pollens augmented in dogs by virus vaccines. Am J Vet Res 1983; 44:440.

12. Ovary Z. IgE production and suppression in mice. Int Arch Allergy Appl Immunol 1981;66(Suppl 1):8.

13. Tada T, Taniguchi M, Okumura K. Regulation of homocyto- tropic antibody production I:n the rat. II. Effect of x-irradiation. J Immunol 1971;106:1012.

14. Katz D. IgE antibody responses in vitro: from rodents to man. Progr Allergy 1982;32:105.

15. Saxon A, Kaplan M, Stephens RH. Isotype-specific B-lymphocytes that produce IgE in vitro when stimulated by pokeweed mitogen. J ALLERGY CLIN IMMUNOL 1980;66:233.

16. Tada T. Regulation of reaginic antibody formation in animals. Prog Allergy 1975;19:122.

17. Katz DH. The allergic phenotype: manifestation of “allergic break-through” and imbalance in normal damping of IgE antibody production. Immunol Rev 1978;41:77.

18. Levine BB, Vaz NM. Genetic control of reagin production in mice. Fed Proc 1971;30:4.

19. Chiorazzi N, Fox DA, Katz DH. Hapten-specific IgE antibody responses in mice. VII. Conversion of IgE “non-responders” by elimination of suppressor T-cell activity. J Immunol 1977;118:48.

20. Piersol JM, Kral K, Frick OL. Effect of attenuated measles virus vaccine on modulation of T-lymphocyte subsets. J AL- LERGY CLIN IMMUNOL 1983;71:139.

21. Leskowitz S, Waksman BH. Studies in immunization. I. Effect of route of injection of bovine serum albumin in Freund’s adjuvant on production of circulating antibodies and delayed hypersensitivity. J Immunol 1960;84:58.

22. Katz DH, Bargatze RF, Bogowitz CA, Katz LR. Regulation of IgE antibody production by serum molecules. IV. Complete Freund’s adjuvant induces both enhancing and suppressive activities detectable in the serum of high and low responder mice. J Immunol 1979;122:2184.

23. Ishizaka K, Ishizaka T, Hombrook NM. Physicochemical prop- erties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. J Immunol 1966;97:75.

24. Johansson SGO, Bennich H, Wide L. A new class of immunoglobulin in human serum. Immunology 1968;14:265.

25. Johansson SGO, Mellbin T, Vahlquist B. Immunoglobulin levels in Ethiopian preschool children with special reference to high concentration of immunoglobulin E (IgND). Lancet 1968;1:1118.

26. Grr TSC. Potentiated reagin response to egg albumin in Nip- postrongylus brasiliensis infected rats. Immunology 1971; 20:185.

27. Suemura M, Ishizaka K. Potentiation of IgE response in vitro by T-cells from rats infected with Nippostrongylus brasiliensis. J Immunol 1979;123:918.

28. Yodoi J, Ishizaka K, Ishizaka T. Lymphocytes bearing Fc receptors for IgE. II. Induction of Fc-receptor bearing rat lymphocytes by IgE. J Immunol 1979;123:455.

29. Yodoi I, Hirashima M, Ishizaka K. Regulatory role of IgE binding factors from rat T-lymphocytes. II. Glycoprotein nature and source of IgE-potentiating factor. J Immunol 1980; 125: 1436.

30. Yodoi J, Hirashima M, Ishizaka K. Lymphocytes bearing Fc receptors for IgE. V. Effect of tunicamycin on the formation of IgE potentiating factor and IgE suppressive factor by ConA activated lymphocytes. J Immunol 1981;126:877.

31. Sampson H. Prospects for control of the IgE antibody response. Pediatr Clin North Am 1983;30:773.

32. Malkiel D, Hargis BJ. Anaphylactic shock in the pertussis- vaccinated mouse. J Allergy 1952;23:352.

33. Morse JH, Kong AS, Lindenbaum J, Morse SI. The mitogenic effect of the lymphocytosis-promoting factor from Borderella perfussis on human lymphocytes. J Clin Invest 1977;50:683.

34. Munoz JA, Bergman RK. Borderella pertussis: immunological and other biological activities. In: Rose N, ed. Immunology, series 4. New York: Marcel Dekker, 1977:123.

35. Hirashima M, Yodoi J, Ishizaka K. Formation of IgE-binding factor by rat T-lymphocytes. II. Mechanisms of selective formation of IgE-potentiating factor by treatment with Borderella pertussis vaccine. J Immunol 1981;127: 1804.

36. Ishizaka K. Regulation of IgE synthesis. Ann Rev Immunol 1984;2:159.

37. Yodoi J, Hirashima M, Bloom BR, Ishizaka K. Formation of IgE-binding factors by rat T-lymphocytes. I. Induction of IgE- binding factors by poly I:C and interferon. J Immunol 1981;127:1579.

38. Uede T, Sandberg K, Bloom BR, Ishizaka K. IgE-binding factors from mouse T-lymphocytes. I. Formation of IgE-binding factors by stimulation with homologous IgE and interferon. J Immunol 1983;130:649.

39. Uede T, Ishizaka K. IgE-binding factors from mouse T-lymphocytes. II. Strain differences in the nature of IgE-binding factors. J Immunol 1984;133:359.

40. Frick OL, Mills J. Sendai virus-induced IgE antibody production in the mouse. J ALLERGY CLM IMMUNOL 1980;65:166.

41. Saryan JA, Leung DV, Geha RS. Induction of human IgE synthesis by a factor from T-cells of patients with hyper IgE status. J Immunol 1983;130:242.

42. Fitzpatrick FA, Stringfellow DA. Virus and interferon effects on cellular prostaglandin biosynthesis. J Immunol 1980; 125:431.

43. Empey DW, Laitinen LA, Jacobs L, Gold WM, Nadel JA. Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory infection. Am Rev Respir Dis 1976; 113:131.

44. Busse WW. Decreased granulocyte response to isoproterenol in asthma during upper respiratory infections. Am Rev Respir Dis 1977;115:783.

45. Ida S, Hooks JJ, Siraganian RP, Notkins AL. Enhancement of IgE-mediated histamine release from human basophils by viruses: role of interferon. J Exp Med 1977;145:892.

46. Welliver RC, Wong RT, Sun M, Middleton E Jr, Vaughn RS, Ogra DI. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med 1981;305:841.

effect of respiratory and other virus infections on ige immunoregulation

Documents