AEGiS-13IAC: Poor CD4+ T cell responses after suppression of HIV replication may reflect thymic failure.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Poor CD4+ T cell responses after suppression of HIV replication may reflect thymic failure.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA283)

Teixeira L, Valdez H, Patki A, Gross B, Koup R, McCune J, Hellerstein M, Badley A, Lederman M
L. Teixeira, Case Western Reserve University, 2061 Crnell Rm 301B, Cleveland, OH 44106, United States, Tel.: +1 216 844 2057, Fax: +1 216 844 5523, E-mail: valdez.hernan@clevelandactu.org

INTRODUCTION: We performed a cross-sectional analysis to compare patients with sustained virologic responses and large CD4+ cell responses (CD4+ cell rise of at least 200 cells/uL, responders) and patients with poor CD4+ cell responses (CD4+ cell rise less than 100 cells/uL; poor-responders) after HAART.

METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 10 responders (R) and 7 poor-responders (NR) with median ages of 38 yrs. and 45 yrs., respectively.Lymphocyte subsets were analyzed by flow cytometry. Lymphocyte proliferation (LP) was measured by 3H-thymidine incorporation after stimulation with different antigens and mitogens. Thymus size was measured by CT scan. Lymphocyte production was measured by H3 incorporation.

RESULTS: After HAART, R had higher median CD4+ cell counts (585 vs. 305 cells/uL); P = 0.001 and CD8+ cell counts (1147 vs. 678 cells/uL) than NR; P = 0.01. The mean frequency of lymphocytes undergoing spontaneous apoptosis was not different in NR (15+ 9%) and R (10+ 5%, P = 0.20). More R ha positive LP responses (stimulation index > 3) after MAC stimulation than NR (80% vs. 14%; P = 0.01). R had a higher % of CD4+ naive cells (46% vs. 26%, P = 0.07) and fewer Fas+ (CD95+) CD8+ T cells (21% vs. 33%, P = 0.02) than NR. Minimal thymic tissue was present on CT scan in 7/7 NR whereas abundant thymic tissue was seen in 7/10 R (P = 0.01). Lymphocyte production and telomere length data will be presented.

CONCLUSION: Patients with poor CD4+ T cell increases after HAART have: smaller thymuses, fewer circulating naive CD4+ T cells; a greater frequency of activated CD4+ and CD8+ T cells. Thymic insufficiency, evidenced by smaller thymic size, fewer circulating naive CD4+ cells, and a lower frequency of TRECs in circulating CD4+ cells, may be a major cause for the failure to increase circulating CD4+ after adequate control of viral replication.

Keywords: AEGIS, Antigens, CD4, Thymus Gland, T-Lymphocytes, HIV Infections, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes, CD4 Lymphocyte Count, Virus Replication, CD8-Positive T-Lymphocytes, HIV Seropositivity, Antigens, CD95, Lymphocyte Subsets, Cross-Sectional Studies, Human, immunology, virology
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TuOrA283