Cytotoxic granule release dominates gag-specific CD4+ T-cell response in different phases of HIV infection.

Abstract

BACKGROUND:

The activity of virus-specific T lymphocytes, among which those capable of a polyfunctional response against the viral protein gag, is crucial to control HIV infection.

OBJECTIVE:

The objective of this study is to investigate the polyfunctionality of gag-specific T cells in different phases of HIV infection, analyzing markers related to T-helper cell 1 (Th1) and degranulation/cytotoxicity, and the production of Th1 cytokines in peripheral blood lymphocytes from patients experiencing an acute primary infection, long-term nonprogressors, patients naive for antiretroviral drugs, and patients taking HAART.

MATERIALS AND METHODS:

Cells were stimulated with a pool of gag-derived peptides or with a superantigen (staphylococcal enterotoxin B). Using eight-color polychromatic flow cytometry, we analyzed the expression of interleukin-2, interferon-gamma, CD154, and CD107a by CD4 and CD8 T cells.

RESULTS:

The main finding was that in all HIV-positive patients, about half gag-specific CD4 T cells were CD107a, that is, able to degranulate. CD4CD154 cells unable to produce Th1 cytokines were the second most represented population. Truly polyfunctional CD4 T cells were very rare and present only in a few long-term nonprogressors. Superantigen stimulation showed that CD4 T lymphocytes from all patients displayed a typical Th response, including interleukin-2 and interferon-gamma production, lacking CD107a expression.

CONCLUSION:

In all the aforementioned phases of HIV infection, the large majority of gag-specific CD4 T lymphocytes cannot be identified by the sole expression of interleukin-2 and interferon-gamma, which is early impaired. Degranulation and helper functions other than Th1 cytokine production are the predominant features of HIV-specific CD4 lymphocytes.

• Authors: Elisa Nemes, Linda Bertoncelli, Enrico Lugli, Marcello Pinti, Milena Nasi, Lisa Manzini, Serena Manzini, Francesca Prati, Vanni Borghi, Andrea Cossarizza, Cristina Mussini
• Journal: AIDS (London, England) (AIDS) Vol. 24 Issue 7 Pg. 947-57 (Apr 24 2010) ISSN: 1473-5571 [Electronic] England
• PMID: 20179574 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gene Products, gag

Topics

• Adult
• Aged
• Blotting, Western
• CD4-Positive T-Lymphocytes (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Cytotoxicity, Immunologic (immunology)
• Female
• Flow Cytometry
• Gene Products, gag (immunology, metabolism)
• HIV Infections (immunology)
• HIV-1 (immunology)
• Humans
• Immunity, Cellular
• Male
• Middle Aged
• Viral Load
• Young Adult