AEGiS-11IAC: Mechanisms of CD8+ T cell dysfunction in HIV.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Mechanisms of CD8+ T cell dysfunction in HIV.

Int Conf AIDS 1996 Jul 7-12; 11:225 (abstract no. Tu.A.381)
Lewis DE, Rahmati S, Yang L, Lloyd T, Bennett T, Ng Tang D, Schober W; Immunology Section, Baylor College of Medicine, Houston, TX, USA. Fax: (713) 798-7949.

OBJECTIVE: To examine mechanisms responsible for phenotypic and functional abnormalities of CD8+ T-cells associated with HIV progression.

METHODS: Phenotypic analyses were done using three color flow cytometry. Functional studies were performed by proliferative and cytokine assays.

RESULTS: Functional abnormalities of CD8+ T cells have been associated with increases in anergic and apoptotic cells and loss of CD8+ CTL and the protective CD38-DR+ subpopulation. Analyses of CD8+ T cell subpopulations in HIV+ patients revealed a strong correlation between loss of CD4+ T cells and the loss of the protective CD38-DR+ population (r=0.933) and CD8+ T cells with the important activation marker, CD28 (r=0.838). A major hypothesis suggests that a cytokine switch from a T1 to T2 occurs during HIV. To determine whether T2 cytokines affect CD8 phenotype and function, we examined the effect on normal CD8+ T cells. IL-4 reduced CD28 surface expression and message on CD8+ T cells by 50% and reduced their capacity to proliferate in response to T cell stimulation. Loss of CD28 also reduced the ability to make IL-2. Because the predominant population of CD8+ T cells in HIV+ persons with low CD4 counts are CD28-, we investigated whether stimulated CD8+ subpopulations produce different cytokines. All CD8+ subpopulations make IFN-gamma, whereas bright CD28+ cells make high amounts of IL-2 and lower amounts of IL-4. Cells with less CD28 make less IL-2 and no IL-4.

CONCLUSIONS: The loss of ability to contain HIV by CD8+ T cells in vivo may be related to loss of CD28 molecules. Cytokine environment may modulate CD28 loss, resulting in loss of proliferative ability, changes in cytokine production, and loss of CD8+ CTL or other protective mechanisms.

Keywords: AEGIS, Antigens, CD8, Antigens, CD28, T-Lymphocytes, HIV, CD8-Positive T-Lymphocytes, T-Lymphocyte Subsets, Interleukin-2, Interleukin-4, CD4-Positive T-Lymphocytes, HIV Infections, Cytokines, Flow Cytometry, Receptors, Interleukin-2, T-Lymphocytes, Cytotoxic, HIV-1, Human, ICA11

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