title: The duration of exposure to HIV modulates the breadth and the magnitude of HIV-specific memory CD4+ T cells.
abstract: The impact of exposure to Ag on the development and maintenance of human CD4(+) memory T cells in general and HIV infection in particular is partially understood. In this study, we measured HIV-specific CD4(+) T cell proliferative responses against HIV proteins and derived peptides one year after highly active antiretroviral therapy initiation in 39 HIV-infected patients who initiated therapy at different times following infection. We show that a brief exposure to HIV of <1 month does not allow the generation of significant detectable frequencies of HIV-specific CD4(+) memory T cells. Patients having prolonged cumulative exposure to high viral load due to therapy failures also demonstrated limited HIV-specific CD4(+) T cell responses. In contrast, patients exposed to significant levels of virus for periods ranging from 3 to 18 mo showed brisk and broad HIV-specific CD4(+) T cell responses 1 year following the onset of therapy intervention. We also demonstrate that the nadir CD4(+) T cell count before therapy initiation correlated positively with the breadth and magnitude of these responses. Our findings indicate that the loss of proliferative HIV-specific CD4(+) T cell responses is associated with the systemic progression of the disease and that a brief exposure to HIV does not allow the establishment of detectable frequencies of HIV-specific memory CD4(+) T cells.
authors.affiliation: Laboratoire d'Immunologie, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Souheil-Antoine
authors.initials: SA
authors.lastname: Younes
authors.forename: Lydie
authors.initials: L
authors.lastname: Trautmann
authors.forename: Bader
authors.initials: B
authors.lastname: Yassine-Diab
authors.forename: Lena H
authors.initials: LH
authors.lastname: Kalfayan
authors.forename: Anne-Elen
authors.initials: AE
authors.lastname: Kernaleguen
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Cameron
authors.forename: Rachid
authors.initials: R
authors.lastname: Boulassel
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Stern
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Zvi
authors.initials: Z
authors.lastname: Grossman
authors.forename: Alain R
authors.initials: AR
authors.lastname: Dumont
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
mesh_terms: D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D017124:Conserved Sequence; D015683:Gene Products, gag / Q000737:chemistry; D015693:Gene Products, nef / Q000737:chemistry; D015696:Gene Products, tat / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D013379:Substrate Specificity; D013997:Time Factors; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015683:Gene Products, gag; D015693:Gene Products, nef; D015696:Gene Products, tat; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus