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248 Anti-HIV-1 CD4+and CD8+T-Cell Responses in Chronically HIV-1-Infected Patients Treated with HAART: Relevance for Specific Immunotherapy
N. Daniel*1,4, G. Pialoux2, H. Gahery1 M. Andrieu1, T. NGuyen2, P. M. Girard2 W. Rozenbaum2, H. Gras-Masse3, D. Sicard4, D. Salmon4, and J. G. Guillet1
1ICGM, Paris, France; 2 Hôsp. Rothschild, Paris, France; 3 Inst. Pasteur, Lille, France; and 4 Hôsp. Cochin, Paris, France
Background: In chronically HIV-1-infected patients, specific CD4+ proliferative responses are usually weak, whereas specific CD8+ responses are highly polyclonal. Here, we described the baseline values of anti-HIV CD4+ and CD8+ responses in 24 HIV-1-infected patients receiving HAART with undetectable viral load and CD4+350/mm3. These evaluations were done prior immunization of these patients with lipopeptides derived from HIV-1 proteins.
Methods: Anti-HIV CD4+ proliferative responses were measured by 3H-thymidine incorporation in long peptide-stimulated PBMC cultures. Anti-HIV CD8+ responses were measured by IFNg ELISPOT assay, which enables detection of the frequency of IFNg spot-forming cells after stimulation with small peptides and number of recognized epitopes.
Results: Before immunization, the mean CD4+ cell count was 644/mm3 and 6/24 patients had CD4+ nadir <200/mm3. Eight of 24 had noninterpretable results for CD4+ responses. Nine of the 18 with interpretable results had CD4+ proliferative responses against one or more peptide. Polyclonal responses were detected in 5/9 patients of which 4 had a stimulation index (SI) >10. These results were independent of the CD4+ nadir. Patients had preferentially (7/9) proliferating responses to Gag 253(284 of which 3 had great magnitude (SI >10). CD8+ responses were absent in 9/24 patients and only 2/24 had polyclonal responses against >4 epitopes.
Conclusions: We confirm that Gag 253-284 is a HLA-DR highly cross-reactive peptide in chronically HIV-1-infected patients treated with HAART and a potentially important component in therapeutic and prophylactic immunotherapy. At least 50% of these patients had memory CD4+ that were able to proliferate against HIV-1 antigenic peptides, and half of them had polyclonal responses. Contrary to chronically HIV-1-infected patients without anti-retroviral treatment, anti-HIV-1 CD8+ responses were absent in a great number (40%) of treated patients and only 8% had highly polyclonal responses. Since highly polyclonal anti-HIV CD8+ responses seem to be associated with a better clinical status, we will next study the impact of specific immunization on the expansion of polyclonality and on the restoration of potentially altered cytotoxic functions.
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