title: Presence of HIV-1 Gag-specific IFN-gamma+IL-2+ and CD28+IL-2+ CD4 T cell responses is associated with nonprogression in HIV-1 infection.
abstract: HIV immunity is likely CD4 T cell dependent. HIV-specific CD4 T cell proliferative responses are reported to correlate inversely with virus load and directly with specific CD8 responses. However, the phenotype and cytokine profile of specific CD4 T cells that correlate with disease is unknown. We compared the number/function of Gag p24-specific CD4 T cells in 17 HIV-infected long-term nonprogressors (LTNPs) infected for a median of 14.6 years with those of 16 slow progressors (SPs), also HIV infected for a median of 14 years but whose CD4 count had declined to <500 cells/ micro l. Compared with SPs, LTNPs had higher numbers of specific CD4s that were double positive for IFN-gamma and IL-2 as well as CD28 and IL-2. However, CD4 T cells that produced IL-2 alone (IL-2(+)IFN-gamma(-)) or IFN-gamma alone (IFN-gamma(+)IL-2(-)) did not differ between LTNPs and SPs. The decrease in p24-specific CD28(+)IL-2(+) cells with a concomitant increase of p24-specific CD28(-)IL-2(+) cells occurred before those specific for a non-HIV Ag, CMV. p24-specific CD28(-)IL-2(+) cells were evident in LTNPs and SPs, whereas the CMV-specific CD28(-)IL-2(+) response was confined to SPs. The difference between LTNPs and SPs in the Gag p24 IFN-gamma(+)IL-2(+) response was maintained when responses to total Gag (p17 plus p24) were measured. The percentage and absolute number of Gag-specific IFN-gamma(+)IL-2(+) but not of IFN-gamma(+)IL-2(-) CD4s correlated inversely with virus load. The Gag-specific IFN-gamma(+)IL-2(+) CD4 response also correlated positively with the percentage of Gag-specific IFN-gamma(+) CD8 T cells in these subjects. Accumulation of specific CD28(-)IL-2(+) helpers and loss of IFN-gamma(+)IL-2(+) CD4 T cells may compromise specific CD8 responses and, in turn, immunity to HIV.
authors.affiliation: Department of Immunology, Guy's, King's, and St. Thomas' School of Medicine and Dentistry, King's College London, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Boaz
authors.forename: Anele
authors.initials: A
authors.lastname: Waters
authors.forename: Shahed
authors.initials: S
authors.lastname: Murad
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Easterbrook
authors.forename: Annapurna
authors.initials: A
authors.lastname: Vyakarnam
mesh_terms: D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D007376:Interleukin-2; D007371:Interferon-gamma