AEGiS-12IAC: Peripheral expansion of CD8+CD28- lymphocytes in the blood of SIVmac251 infected macaques correlates with CD4 depletion and is associated with T-cell functional defects.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Peripheral expansion of CD8+CD28- lymphocytes in the blood of SIVmac251 infected macaques correlates with CD4 depletion and is associated with T-cell functional defects.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:26 (abstract no. 11220)

Lebel-Binay S, Vaslin B, Gigout L, Le Grand R, Fradelizi D, Dormont D
CEA Service de Neurovirologie DSV-DRM, Fontenay, AUX Roses, France.

BACKGROUND: Phenotypical and functional analysis of peripheral T lymphocytes from 10 macaques chronically infected with SIVmac251.

METHODS: Ten cynomolgus macaques were inoculated i.v. with 4 AID50 of a pathogenic SIVmac251 isolate. A group of non-infected cynomolgus macaques in the same range of age and same origin was used as control. Peripheral CD4+ and CD8+ T lymphocytes counted by flow cytometry and were phenotyped for expression of several surface markers. At the same time, PBMC were stimulated with ConA, anti-CD3 mAbs, or anti-CD3 + anti-CD28 mAbs. Three days after stimulation, the proliferative response and the production of lymphokines (IL-2, IFN gamma) were measured.

RESULTS: Expression of CD28 molecule on T lymphocytes from non-infected monkeys was found to be similar than that found on human T lymphocytes (86 ± 4% of CD4 and 57 ± 7% of CD8). In infected monkeys, we observed a progressive decrease of the CD28+ T cells (after 3 years, 25 ± 15% of CD8). Our results demonstrate a strong correlation between the progression of the disease (CD4+ cell counts and plasma viral load) and the expansion of the CD8+CD28- population in the blood. The majority of these cells express CD45RA (naïve) and CD29 (memory) markers, are CD7 negative, contain CD69 positive cells and CD38 bright cells. Stimulation of PBMCs in vitro demontrates progressive alteration of T cell response, first to the costimulation of CD28, then to CD3, and eventually to ConA stimulation. In the same time, the production of lymphokines in response to these stimulations was reduced. CD28 negative CD4+ T cells were also found to accumulate in some macaques with very low CD4+ cell counts.

CONCLUSIONS: As shown in humans infected by HIV-1, CD28- T cells do accumulate in the blood of SIV infected macaques. This expansion is progressive, correlates with the decrease of CD4+ T cell counts and plasma viral load and is associated with defects in the proliferative response and cytokines production of T cells after stimulation. This peripheral accumulation of CD28- T cells may be a direct consequence of a long term antigen stimulation and/or a sequestration of "immuno-competent" T cells in lymphoid organs, and may constitute a good marker of immunodeficiency in non-human primate models of AIDS.

Keywords: AEGIS, Antigens, CD4, T-Lymphocytes, Antigens, CD28, CD8-Positive T-Lymphocytes, Antigens, CD8, HIV-1, Macaca, CD4 Lymphocyte Count, Antigens, CD3, Antigens, CD45, Viral Load, Antigens, CD, Antigens, Differentiation, T-Lymphocyte, Interleukin-2, SIV, Acquired Immunodeficiency Syndrome, Flow Cytometry, Simian Acquired Immunodeficiency Syndrome, CD69 antigen, Animal, Human, In Vitro, blood, immunology, ICA12
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