AEGiS-08IAC: HIV glycoprotein gp120 induces anergy in human T4 lymphocytes, not in chimpanzee lymphocytes.

8th International AIDS Conference

Amsterdam, Netherlands — July 19-24, 1992

HIV glycoprotein gp120 induces anergy in human T4 lymphocytes, not in chimpanzee lymphocytes.

Int Conf AIDS 1992 Jul 19-24; 8:We53 (abstract no. WeA 1046)
Di Rienzo AM, Furlini G, Olivier R, Ferris S, Montagnier L; Unite d'Oncologie Virale, Institut Pasteur, Paris, France.

OBJECTIVES: We investigated the unresponsiveness to mitogenic stimulation of human lymphocytes triggered by HIV-1 or gp120. Moreover, in order to assess the importance of this anergy phenomenon, the proliferation of chimpanzee peripheral blood lymphocytes triggered by gp120 has been analyzed as well.

METHODS: Before or after the activation by different stimuli, lymphocytes have been incubated with purified and heat-inactivated HIV-1 particles or recombinant gp120. Proliferation has been evaluated by 3H thymidine incorporation on quadruplicate samples. Expression of activation markers (CD25, CD71), gp120-CD4 interaction and the lymphocytes population used, have been analyzed by flow cytometry. Several experiments have been performed with the T helper population selected by negative panning and preincubated with gp120 in serum free medium. DNA has been analyzed by agarose electrophoresis.

RESULTS: Incubation of resting lymphocytes with HIV-1 or gp120 strongly inhibits their response to proliferative stimuli. On the other hand, this phenomenon is not observed in preactivated lymphocytes. The inhibition is still more pronounced if gp120 interacts with purified T helper cells. The responses of human lymphocytes to PHA + IL2, PHA + IL4, PHA + IL6, PMA + Ionomycine, anti-CD3 and anti-CD2 are all inhibited by gp120. No evidence of apoptosis has been noted during the experiments. Only a slight down-modulation of the receptors for IL2 (CD25) and transferrin (CD71) correlates with the inhibition of proliferation. Such inhibition has not been obtained on chimpanzee lymphocytes triggered by gp120 before their activation by PHA and IL2.

CONCLUSIONS: The triggering of CD4 without CD3 co-stimulation can have important consequences on lymphocyte activation. Our results indicate that anergy follows gp120-CD4 interaction and that a large spectrum of activation stimuli are inhibited. The fact that chimpanzee lymphocytes are not inhibited may suggest the importance of the phenomenon "in vivo". Although soluble gp120 seems unable to induce apoptosis, we cannot exclude that anergic cells are programmed for this phenomenon.

Keywords: AEGIS, CD4-Positive T-Lymphocytes, Lymphocytes, Antigens, CD4, Pan troglodytes, HIV-1, Lymphocyte Activation, Antigens, CD3, Interleukin-2, Glycoproteins, Receptors, Interleukin-2, Antigens, CD, Phytohemagglutinins, T-Lymphocytes, Helper-Inducer, CD71 antigen, Animal, Human, immunology, ICA8
920719
WeA1046