sa.116. expression of toll-like receptors on t-cells, b-cells and monocytes from hiv infected...
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withdrawal of the drugs. Due to the relapsing characteristicof the disease in these patients we thought of a mendeliansusceptibility to mycobacterial disease. Slight decrease in Tlymphocytes for patient #1 with normal lymphoproliferationfor mitogens and Candida Ag, but low response to PPD. IFN-gammawas low for the 2 patients, expression of IL-12 p40 andIFN-g R1 was normal, but the expression o IL-12Rb1 was lowfor patient #2 under basal conditions, improving significantlyafter stimulation with BCG. The expression of IL-12 Rb2 andSTAT-1 were normal, as well as NADPH oxidase function.Patient #2 showed a compound heterozygous mutation of IL-12 Rb1 (R173W substitution and a deletion of 17 bp on exon 9on the other allele). The studies carried out to date have beenfruitful, initiating the genetic dissection of protectiveimmunity against a variety of mycobacterial species innatural conditions of infection. The human model haspotential uses beyond the study of mycobacterial infectionsand may well become a model of choice for the investigationof immunity to infectious agents.
doi:10.1016/j.clim.2006.04.346
Sa.115. Are HIV-1-Induced Non-Classical MHCMolecules On CD4+T-Cells and Elevated Levels ofGamma-Delta CTLs in the Peripheral Blood of AIDSPatients Two Complementary Pieces of bCD4+ T-CellDepletionQ Puzzle?Sardar Sindhu,1 Jose Menezes,2 Maud Loignon,1 Lise Cyr,1
Richard Morisset,1 Emil Toma.1 1Microbiology and InfectiousDiseases, Hotel-Dieu Hospital, Montreal, QC, Canada; 2Labof Immunovirology, St. Justine Hospital, Montreal, QC,Canada.
Progression of acquired immunodeficiency syndrome(AIDS) is characterized by depletion of CD4+T-cells andenhancement of virus load (VL). Mechanisms leading toCD4+T-cell depletion are central to AIDS pathogenesis. Wealready showed that circulating gamma-delta CTLs from HIVpatients lysed CD4+T-cells. The objective of this study wasto focus on the mechanism of this anti-CD4 cytocidalactivity. A cross-sectional study was performed using bloodsamples from 20 HIV-1/AIDS patients and 10 HIV-1 seroneg-ative controls. In vitro activated gamma-delta cytotoxic Tlymphocytes (CTLs) from AIDS patients were used aseffectors against autologous/allogeneic CD4+T-cells includ-ing a panel of other human cells in [51]Cr-release cytotoxicassays. The gamma-delta CTLs lysed all targets used and apositive correlation was found between anti-CD4 cytocidalactivity and VL of CTL donors (r = 0.83; P b 0.01).Immunophenotyping revealed that Vdelta-1 CTLs were thepredominant effectors involved in cytolysis. Further, we alsofound that MICA/B surface expression on CD4+T-cells fromAIDS patients was significantly enhanced as compared withcontrols (P b 0.05). Gamma-delta TCR blocking by specificmonoclonal antibodies (mAbs) and/or labeling of CD4+T-cells with anti-MICA/B Abs abrogated this cytolysis signifi-cantly (P b 0.0001). It was therefore inferred that gamma-delta CTLs lysed CD4+T-cells in AIDS patients through bothTCR-dependent and TCR-independent mechanisms while therecognition of HIV-1-induced MICA/B MHC molecules on
these targets represents a novel mechanism of CD4+T-celldepletion in AIDS patients.
doi:10.1016/j.clim.2006.04.347
Sa.116. Expression of Toll-Like Receptors On T-Cells,B-Cells and Monocytes from HIV Infected Patients.Simone Fonseca,1,3 Adriana Coutinho-Silva,1,3
Rajendranath Ramasawmy,1,3 Luis Fonseca,2,3
Eliane Mairena,1,3 Kellen Fae,1,3 Sandra Moraes,1,3
Edecio Cunha-Neto,2,3 Jorge Kalil.2,3 1Laboratory ofImmunology, Heart Institute, University of Sao Paulo, SaoPaulo, Brazil; 2Division of Clinical Immunology and Allergy,School of Medicine, University of Sao Paulo, Sao Paulo,Brazil; 3Institute for Investigation in Immunology,Millenium Institute-CNPq, Sao Paulo, Brazil.
Toll-like receptors (TLRs) are pathogen associated mole-cular pattern receptors that play an important role in both theinnate and adaptative immunity to infection agents. Recently,it has been shown that activation through TLR2 and TLR4 canincreaseHIVreplication in infected cells. Here,we investigatethe effects of HIV infection on expression of TLRs on subsets ofperipheral T lymphocytes, B lymphocytes andmonocytes fromHIV infected patients. Fresh PBMC from 5 aviremic patients(CD4 N 400 cells/ul, viral load b 400 copies/ml) and 7 viremic(CD4 N 300 cells/ul, VL N 1000 copies/ml) were stained withfluorochrome labeled monoclonal antibodies to TLR2, TLR4,TLR3 and CD3, CD4, CD8, CD19, CD14 and analyzed by flowcytometry. All patients were free of secondary infections. Ourresults showed that the mean intensity of fluorescence (MFI)of TLR2 of aviremic (AV) and viremic (VR) patients for thefollowing PBMC subsets were: CD4 T-cells AV[27.0], VR[36.6];CD8 T-cells AV[25.2], VR[38.4]; B-cells AV[89.8], VR[156.8];monocytes AV[39.1], VR[29.9]. Similarly, TLR4 expression oncells from AV and VR patients were detected: CD4 AV[71.1],VR[111.3]; CD8 AV[190.2], VR[178.5]; B-cells AV[42.8],VR[30.5]; monocytes AV[66.2], VR[61.1]. The TLR3 expressionwas higher on T-cells from viremic patients compared toaviremic; the MFI to CD4 T-cells were 25.7 (AV) and 373.1 (VR)and to CD8 T-cells were 20.4 (AV) and 237.8 (VR). Inconclusion, our preliminary results suggest that the viremiadoes not correlate with the expression of TLR2 and TLR4 onlymphocytes and monocytes of HIV infected patients. How-ever, viremia seems to modulate the TLR3 on T lymphocytes.
doi:10.1016/j.clim.2006.04.348
Laboratory Immunology
Sa.117. A Critical Role of B7-H1 in Protection of IsletAllografts By Co-Transplanted Hepatic Stellate Cells.Lina Lu,1 Cheng-Hsu Chen,1 Liang-Mou Kuo,1
Wenhan Wu,1 John Fung,2 Shiguang Qian.1 1Immunology,Cleveland Clinic Foundation, Cleveland, OH; 2GenaralSurgery, Cleveland Clinic Foundation, Cleveland, OH.
Successful organ transplantation has been practiced fordecades, but the outcome of cell transplants remains
AbstractsS146