TY - JOUR
T1 - Cytotoxic granule release dominates gag-specific CD4+ T-cell response in different phases of HIV infection
AU - Nemes, Elisa
AU - Bertoncelli, Linda
AU - Lugli, Enrico
AU - Pinti, Marcello
AU - Nasi, Milena
AU - Manzini, Lisa
AU - Manzini, Serena
AU - Prati, Francesca
AU - Borghi, Vanni
AU - Cossarizza, Andrea
AU - Mussini, Cristina
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - AIDS
KW - CD107a
KW - CD154
KW - CD4
KW - Gag
KW - HIV
KW - Long-term nonprogressor
KW - Lymphocyte degranulation
KW - Specific response
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U2 - 10.1097/QAD.0b013e328337b144
DO - 10.1097/QAD.0b013e328337b144
M3 - Article
C2 - 20179574
AN - SCOPUS:77950952763
VL - 24
SP - 947
EP - 957
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 7
ER -