AEGiS-10CROI: Relationship Between Functional and Qualitative Abnormalities within the Pool of HIV-1 Specific Memory CD4 T-cells and Control of HIV-1 Disease.

10th Conference on Retroviruses and Opportunistic Infections

Boston, MA USA - February 10 -14, 2003

Relationship Between Functional and Qualitative Abnormalities within the Pool of HIV-1 Specific Memory CD4 T-cells and Control of HIV-1 Disease.

Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 33
A. Harari , S. Petitpierre, M. Khonkarly, P. A. Bart, G. Pantaleo
Lab of AIDS Immunopathogenesis, Lausanne, Switzerland

BACKGROUND: During chronic HIV infection, HIV-specific CD4 T-cell proliferation is generally lost, but HIV-specific IFN-γ secreting CD4 T-cells can be detected. In the present study, we have investigated new quantitative and qualitative measures of HIV-specific CD4 T-cell immune response and compared with CMV-specific immune response.

METHODS: The secretion of IFN-γ and of Il-2 following specific stimulation (HIV-1 and CMV antigens) was analyzed in peripheral blood and lymph nodes (LN) of 14 HIV-infected progressors with no previous ART, 7 LTNP and 14 HIV-negative donors. Cells were stained with mAbs to CD4, CCR7, CD45RA, CD69, IFN-γ, and Il-2. Ratios between the percentages of virus-specific IL-2 and IFN-γ secreting cells were calculated to identify a quantitative marker of the global CD4 T-cell immune response.

RESULTS: HIV- and/or CMV-specific IFN-γ secreting cells were detected in all individuals in blood and LN. There was no association between the percentages of HIV-specific IFN-γ secreting CD4 T-cells and viremia levels (p > 0.1, n = 21 for both blood and LN). Of interest, by the analysis of the pool of virus-specific CD4 T-cells, a novel population of T-cells, e.g., IFN-γ secreting CD4⁺CD45RA⁺CCR7^- was detected only in LTNP and not in progressors (means: 0.43 vs 0.03%, p = 0.002) for HIV and in all 3 groups of individuals for CMV (All p > 0.5). The percentages of HIV-specific CD45RA⁺CCR7^- CD4 T-cells correlated negatively with viremia levels (r = -0.8, p < 0.01, n = 13). With regards to virus-specific IL-2 secreting CD4 T-cells, CMV-specific Il-2 secreting CD4 T-cells were consistently found in all 3 groups in blood and LN (all p > 0.05) but Il-2 secreting CD4 T-cells were only found in LTNP (means: blood 0.17%, LN 0.14%) and not in progressors (means: blood 0.02%, LN 0.01%, both p < 0.0002) following HIV stimulation. Strong negative correlations were found between viremia levels and the percentages of HIV-specific IL-2-secreting CD4 T-cells in blood and LN (r = -0.8, p < 0.01, n = 21, for both). Of note, there was also a negative correlation between HIV-specific IL-2/IFN-γ ratios and viremia levels (blood r = -0.63, p < 0.01; LN r = -0.82, p < 0.01, n = 21, for both).

CONCLUSIONS: These results demonstrate an abnormal composition of the pool of HIV-specific CD4 T-cells and a selective IL-2 defect of the HIV-specific memory CD4 T-cells in both blood and LN. These parameters represent correlates of immune protection better than CD4 T-cell proliferation.

030210
33

Copyright © 2003 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.