AEGiS-11IAC: The peripheral deletion of Vgamma9/Vdelta2 in HIV-infected donors is associated with a proliferative anergy to non-peptidic ligand TUBAg and a defect in cytokine secretion.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

The peripheral deletion of Vgamma9/Vdelta2 in HIV-infected donors is associated with a proliferative anergy to non-peptidic ligand TUBAg and a defect in cytokine secretion.

Int Conf AIDS 1996 Jul 7-12; 11:5 (abstract no. Mo.A.140)
Boullier S, Poccia F, Lecoeur H, Fournieo JJ, Gougeon ML; Unite D'oncologie Virale, Institut Pasteur, Paris, France.

OBJECTIVES: Since we have previously reported a strong peripheral decrease of peripheral Vdelta2 gammaT lymphocytes in asymptomatic HIV-infected donors, the objective of this study was to characterize whether this decrease was associated with an alteration of the repertoire and the functions of these gamma cells.

METHODS: The rearrangements of Vdelta2 TCR were analysed by PCR using specific oligonucleotides. CDR3 size distribution was determined on an Automatic DNA sequencer using fluorescent Jdelta's oligonucleotides. The proliferative response and cytokine synthesis of peripheral Vdelta2 T cells after stimulation with several specific ligands(Mycobacterium Tuberculosis lysat, Daudi or TUBAg-1) was studied by FACS. To determine the nature of cytokine synthesized by targeted subsets, we developed a cytofluorimetric method consisting in intracellular staining, with specific anti-cytokine mAbs, of several cell subsets defined by membrane staining. Results and discussion: The study of the CDR3 size distribution of Vdelta2 T cells revealed that the peripheral deletion was not oligoclonal or monoclonal since the CDR3 profiles were comparable to that of control donors, and though remained polyclonal. Moreover, Vdelta2 T cells from HIV-infected donors were not found more susceptible to apoptosis than Vdelta2 T cells from control donors. Interestingly, functional studies revealed that in 50% of the tested asymptomatic HIV+ donors, Vdelta2 T cells did not proliferate in response to specific stimulations including M.tuberculosis and the natural ligand TUBAg-1. This Vdelta2 T cell anergy persisted even in the presence of exogenous IL-2 and was frequently correlated with a defect in CD25 expression in this subset. These results suggest that the deletion and the anergy of the V2 T cell subset was consecutive to an in vivo chronic polyclonal activation by a cellular ligand induced or modified by HIV-infection. On the other hand, analysis of cytokine secretion revealed that, after specific stimulation with TUBAg-1, Vdelta2 T cells from control donors synthesized high levels of IFNgamma and TNFalpha but no IL2 or IL4. In Vdelta2 responder HIV-infected donors, the cytokine profile was similar to that obtained for control donors. On the opposite, in Vdelta2 anergic donors, Vdelta2 T cells synthesized low levels of TNFalpha and IFNgamma, cytokines known to be essential for the antimycobacterial response. Therefore, the proliferative anergy of Vdelta2 T cells to TUBAg-1 was found associated with a defect in the anti-mycobacterial helper function of this subset. The quantitative and qualitative alterations of Vdelta2 T cells in HIV-infected persons might have important consequences on the cellular immunity against M.Tuberculosis infection, whose incidence is high at the AIDS stage.

Keywords: AEGIS, Cytokines, T-Lymphocytes, T-Lymphocyte Subsets, Mycobacterium tuberculosis, HIV Infections, Interleukin-2, Bodily Secretions, Ligands, Interleukin-4, Mycobacterium, Acquired Immunodeficiency Syndrome, secretion, ICA11

960707
MoA140