Session 7Oral Abstract Presentations Immune Responses to HIV Session Day and Time: Tuesday 10 am - 12:15 pm Presentation Time: 11:30 Room: Ballroom B
33 Relationship Between Functional and Qualitative Abnormalities within the Pool of HIV-1 Specific Memory CD4 T-cells and Control of HIV-1 Disease 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-g 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-g 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-g, and Il-2. Ratios between the percentages of virus-specific IL-2 and IFN-g secreting cells were calculated to identify a quantitative marker of the global CD4 T-cell immune response.
Results: HIV- and/or CMV-specific IFN-g secreting cells were detected in all individuals in blood and LN. There was no association between the percentages of HIV-specific IFN-g 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-g 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-g 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.
