Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1–infected subjects with progressive disease: changes after antiretroviral therapy

• Published in: Blood Vol. 103; no. 3; pp. 966 - 972
• Main Authors: Harari, Alexandre, Petitpierre, Stéphanie, Vallelian, Florence, Pantaleo, Giuseppe
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.02.2004; The Americain Society of Hematology
• Subjects: Anti-HIV Agents - therapeutic use; Biological and medical sciences; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cytomegalovirus - immunology; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1; Human viral diseases; Humans; Infectious diseases; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Medical sciences; Prospective Studies; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Immune response; HIV-1 virus; Secretion; Herpesviridae; Cytokine; Retroviridae; AIDS; Betaherpesvirinae; Immune deficiency; Lentivirus; Cell subpopulation; Human cytomegalovirus; Infection; Virus; Treatment; Interleukin 2; Immunological investigation; Viral disease; T-Lymphocyte; Antiviral; Human immunodeficiency virus; Gamma interferon
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-04-1203

HIV-1- and cytomegalovirus (CMV)-specific CD4 T-cell-mediated antiviral immunity was evaluated by assessing the frequency of interleukin 2 (IL-2)- and interferon γ (IFN-γ)-secreting cells following antigen-specific stimulation in blood and lymph node. HIV-1-infected subjects with progressive disease at early stage of infection with no previous history of antiretroviral therapy (ART), subjects with nonprogressive disease, and HIV-negative subjects were studied. On the basis of the ability to secrete IL-2 and IFN-γ, 3 functionally distinct populations of CD4 T cells were identified: (1) IL-2-secreting cells; (2) IL-2/IFN-γ-secreting cells; and (3) IFN-γ-secreting cells. CMV-specific CD4 T cells were almost equally distributed within the 3 functionally distinct cell populations in the 3 study groups as well as HIV-1-specific CD4 T cells in subjects with nonprogressive disease. However, a skewing toward IFN-γ-secreting cells (70% of HIV-1-specific CD4 T cells) was observed in subjects with progressive disease, and IL-2- and IL-2/IFN-γ-secreting cells were almost absent. The frequencies of IL-2- and of IL-2/IFN-γ-secreting HIV-1-specific CD4 T cells were negatively correlated with the levels of viremia. Interestingly, prolonged ART was able to correct the skewed representation of different populations of HIV-1-specific CD4 T cells but was associated with only a partial recovery of IL-2-secreting cells. These results indicate that the composition of the pool of functionally distinct virus-specific CD4 T cells is important for virus control. (Blood. 2004;103:966-972)