11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retrovir Opportunistic Infect 2004 Feb 8-11; 11:(abstract no. 15)

A Harari, F Vallelian, S C Zimmerli, and G Pantaleo
Lab. of AIDS Immunopathogenesis, Lausanne, Switzerland

BACKGROUND: Several studies performed in mice and humans have demonstrated wide heterogeneity of memory CD4 T cells. Multiple phenotypes and a broad spectrum of functions have been observed in different viral infections.

METHODS: We have addressed this issue by analyzing different models of memory CD4 T-cell responses in 18 HIV-1-infected subjects with chronic progressive infection, 7 HIV-1-infected subjects with non-progressive infection, and 50 HIV-negative subjects. We used tetanus toxoid (TT) as a model of memory T-cell response where the antigen is cleared; the Cytomegalovirus (CMV) chronic infection as a model of repetitive antogen exposure and low antigen load; and HIV-1 infection as a model of antigen persistence and high antigen load. Immune responses were characterized using multi-parametric flow cytometry.

RESULTS: The TT-specific CD4 T cells were mostly composed of single IL-2-secreting cells, the 3 distinct cytokine-secreting CD4 T-cell populations (single IL-2, IL-2-IFN-γ and single IFN-γ) were well represented within CMV-specific T cells, and single IFN-γ-secreting cells dominated the HIV-1-specific T-cell response. We then determined the effects of changes in antigen exposure and antigen load within the 3 models of immune response. After re-immunization, we observed a substantial increased (about 5-fold) in the percentage of TT-specific single IL-2- secreting CD4 T cells with a peak at day 11 and, more interestingly, we observed the appearance of IL-2-IFN-γ and single IFN-γ-secreting cells. The newly generated cell populations were CD45RA^-CCR7^- while the single IL-2-secreting CD4 T cells that served as precursors were CD45RA^-CCR7⁺. The large majority (about 90%) of CMV-specific CD4 T cells were single IFN-γ-secreting cells, about 10% were IL-2-IFN-γ-secreting cells, and single IL-2-secreting cells were almost absent during primary CMV infection. The majority of CMV-specific cells were CD45RA^-CCR7^- while the CD45RA⁺CCR7^- cell population, present in chronic infection, was absent. The 3 distinct cytokine secreting CD4 T-cell populations were equally represented in the HIV-1-infected subjects with non-progressive disease and low antigen load or following virus suppression by antiviral therapy in subjects with progressive disease.

CONCLUSIONS: Antigen persistence and antigen load appear to influence substantially the composition of functional and phenotypically distinct CD4 cell populations in different models of immune response.

040208
15

Copyright © 2004 - 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.