AEGiS-11IAC: Possible involvement of peripheral Vdelta1gammadelta T cells in the secretion of TH2 type cytokines in HIV-infected donors.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Possible involvement of peripheral Vdelta1gammadelta T cells in the secretion of TH2 type cytokines in HIV-infected donors.

Int Conf AIDS 1996 Jul 7-12; 11:214 (abstract no. Th.A.163)
Boullier S, Lafeuillade A, Roue R, Gougeon ML; Unite D'oncologie Virale. Institut Pasteur, Paris, France.

OBJECTIVES: We have previously demonstrated a strong peripheral increase of the Vdelta1gammadelta T cell population during HIV infection. TCR repertoire analysis indicated that this expansion was polyclonal and in addition the in vivo expanded Vdelta1T cell subset was in a preactivated state (JI. 1995, 154: 1418). Several studies have reported an imbalance in the profile of cytokines secreted by T cells from HIV+ donors, possibly contributing to disease evolution. In order to define whether the expanded Vdelta1T cell subset contributes to the evolution of the pattern of cytokines secreted in patients, we characterized the potential helper function of this subset and the nature of cytokines they produce following activation.

METHODS: To determine the pattern of cytokines synthesized by peripheral blood lymphocytes, we developped a cytofluorimetric method of intracellular staining with specific anti-cytokines mAbs, associated with cell surface staining of various subsets. PBMC from HIV+ (21 stage II, 12 stage IV) and 20 HIV - donors were stimulated for 12 hours with PHA, PMA and ionomycine and then double stained with anti-cytokine mAbs (IL-2, IL-4, IL-13, IFNgamma and TNFalpha) and mAbs specific for the CD3 moleculeor the Vdelta1 TCR. Results and discussion: In healthy donors, Vdelta1T cells represent a small proportion of blood CD3+ T cells (less than 1%). On the opposite, this population is strongly increased in HIV-infected donors (Vdelta1T cells can represent up to 20% of blood CD3+T cells). The intracellular detection of cytokines confirmed that, in HIV-infected donors, there was a global increase in the number of cells (CD3+ and CD3-) secreting IL4. Characterization of the cytokine profile synthesized by Vdelta1T cells revealed that: 1-Vdelta1T cells from control donors were not able, after polyclonal activation, to synthesize Th1 or Th2 cytokines (IL2, IL4, IL13, IFNgamma and TNFalpha). 2-On the opposite, 50% of Vdelta1T cells from HIV-infected donors synthesized under the same conditions high level of IL4, whereas TNFalpha secreting Vdelta1T cells were weakly increased. None of the other cytokines were detected in Vdelta 1T cells from HIV+ donors. The increase of peripheral Vdelta1 IL4+ T cells was also found in absolute number. This study demonstrates that the selective expansion of peripheral Vdelta1T cells in HIV-infected donors is associated with the selective secretion by this subset of Th2 (IL-4) type cytokines. It further suggests that the expanded Vdelta1 T cells play a role in the induction and/or in the persistence of the Th2 type cytokine profile observed in HIV-infected patients.

Keywords: AEGIS, T-Lymphocytes, Cytokines, Antigens, CD3, Interleukin-4, HIV Infections, Interleukin-2, Bodily Secretions, Receptors, Antigen, T-Cell, gamma-delta, Receptors, Antigen, T-Cell, Antigens, CD28, Interleukin-13, Human, secretion, ICA11

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