74

Preliminary Communications

TUBERCULIN ANERGY AND INFECTIOUS

MONONUCLEOSIS

S. HAIDER M. DE L. COUTINHO

R. T. D. EMOND

Royal Free Hospital Infectious Diseases Unit,Coppetts Wood Hospital, London N10 1JN

R. N. P. SUTTON

Department of Medical Microbiology, King’s CollegeHospital Medical School, London SE5 8RX

Summary Cell-mediated immunity, as assessed

by the response to tuberculin, wasinvestigated in twenty-three patients with infectiousmononucleosis. In eight patients, negative reactionswere observed during acute illness which became

positive during convalescence, suggesting that therehad been a temporary depression of cell-mediated

immunity.INTRODUCTION

THE recognition that the Epstein-Barr (E.B.)virus is the probable causative agent in infectiousmononucleosis 1,2 has led to a resurgence of interest inthis disease.

Immunologically, the most impressive feature ofinfectious mononucleosis is the development of a

medley of "

inappropriate " antibodies which are

probably, in part at least, responsible for the highlevels of immunoglobulins found in this disease.3-5 Thehumoral limb of the immune response thus remainsintact, although functioning somewhat aberrantly.What happens to cell-mediated immunity in the

acute phase of infectious mononucleosis is not well

documented, apart from one report of transientdepression of the tuberculin response.

Tuberculin reactivity is an efferent activity of theT lymphocyte in response to intradermal tuberculin.A positive reaction expresses an intact cell-mediatedimmunity system in an individual who, in the past,has been exposed to Mycobacterium tuberculosis,and non-reactivity in such a person indicates an

abnormality in this system. The conversion from

non-reactivity to a reactive state indicates recoveryfrom a transient immunological depression affectingthis system. We used this simple test to assess thecell-mediated immunity in infectious mononucleosis.

PATIENTS AND METHODS

Patients with clinical features of infectious mono-

nucleosis, including heterophile antibodies and typicalabnormal white blood-cells, were investigated. All were

given an intradermal test of 1/10,000 tuberculin duringthe acute phase of the illness, and this test was repeated 6weeks later. The tests were read after 48 hours and anarea of induration of 8 mm. or over was considered to be

positive.RESULTS

Twenty-three patients with infectious mono-

nucleosis were included in this survey. Eight gavea negative tuberculin reaction during the acute phase

of illness which became positive when they weretested 6 weeks later; five of these eight gave a definitehistory of B.C.G. vaccination. These results (see table)suggest that in a considerable number of patients(35%) there was a transient depression of cell-

mediated immunity during the acute phase of in-fectious mononucleosis:

DISCUSSION

The exact mechanism of this transient depressionof the cell-mediated immune response is not clear.Is it due to virus multiplication in the T lymphocyteswith consequent functional impairment ? E.B. virusparticles are, in vitro, cleared from culturedinfectious-mononucleosis leucocytes within 2-3

months,7,8 but we do not know what happens in vivo;can failure of clearance occur and, if so, could itresult in continued immunosuppression ?

There are further implications of this transient

immunological depression in infectious mono-

nucleosis. The association of the herpes-like E.B. ;

virus with infectious mononucleosis, with Burkitt’s

lymphoma, and with some types of nasopharyngealcarcinoma is now well recognised.4,9 There have beenreports that nucleic acid homologous with that of theR.N.A. Rauscher murine-leukxmia virus has beendetected in Burkitt’s tumour and in nasopharyngeal-carcinoma cells These apparently conflictinggroups of observations may be reconciled if we

accept that depression of cell-mediated immunityby E.B. virus infection (as in infectious mono-

nucleosis) could provide the necessary stimulus to

activate an otherwise dormant virus genome.11The disturbance of cell-mediated immunity in

infectious mononucleosis and in the more frequentasymptomatic infections with the E.B. virus deservesfurther investigation as a possible mechanism forthe induction of malignant change in man.

We are grateful to Dr Hillas Smith for his permission to

include some of the patients admitted under his care.Requests for reprints should be addressed to S. H.

REFERENCES

1. Henle, G., Henle, W., Diehl, V. Proc. natn. Acad. Sci. U.S.A.1968, 59, 94.

2. Niedermann, J. C., Evans, A. S., Subrahmanyan, L., McCollum,R. W. New Engl. J. Med. 1970, 282, 361.

3. Wollheim, F. A., Williams, R. C. ibid. 1966, 274, 61.4. Sutton, R. N. P. J. clin. Path. 1972, 25, suppl. 6, p. 58.5. Sutton, R. N. P., Reynolds, K., Almond, E. J. P., Marston, S. D.,

Emond, R. T. D. Clin. exp. Immun. 1973, 13, 359.6. Jones, J. V. in Proceedings of the Third Symposium on Impaired

Cell-mediated Hypersensitivity in Man (edited by J. F. Jenningsand D. J. Ward); p. 81. Robert Jones and Agnes Hunt OrthopædicHospital Management Committee, Oswestry, 1970.

7. Diehl, V., Henle, G., Henle, W., Kohn, G. J. Virol. 1968, 2, 663.8. Marston, S. D., Almond, E. J. P., Bishun, N. P., Maunsell, E. D.,

Sutton, R. N. P. J. clin. Path. 1972, 25, 701.9. Achong, B. G. ibid. 1972, 25, suppl. 6, p. 51.

10. Kufe, D., Hehlmann, R., Spiegelman, S. Proc. natn. Acad. Sci.U.S.A. 1973, 70, 5.

11. Huebner, R. J., Kelloff, G. J., Sarma, P. S., Lane, W. T., Turner,H. C. ibid. 1970, 67, 366.

12. Siegel, S. Non-parametric Statistics. New York, 1956.