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

Elisa Nemes, Linda Bertoncelli, Enrico Lugli, Marcello Pinti, Milena Nasi, Lisa Manzini, Serena Manzini, Francesca Prati, Vanni Borghi, Andrea Cossarizza, Cristina Mussini

Research output: Contribution to journalArticlepeer-review

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-γ, 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. CD4+CD154+ 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-γ 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-γ, which is early impaired. Degranulation and helper functions other than Th1 cytokine production are the predominant features of HIV-specific CD4+ lymphocytes.

Original languageEnglish
Pages (from-to)947-957
Number of pages11
JournalAIDS (London, England)
Volume24
Issue number7
DOIs
Publication statusPublished - Apr 2010

Keywords

  • AIDS
  • CD107a
  • CD154
  • CD4
  • Gag
  • HIV
  • Long-term nonprogressor
  • Lymphocyte degranulation
  • Specific response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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