title: Preservation of T cell proliferation restricted by protective HLA alleles is critical for immune control of HIV-1 infection.
abstract: HIV-1-infected persons with HLA-B27 and -B57 alleles commonly remain healthy for decades without antiretroviral therapy. Properties of CD8+ T cells restricted by these alleles considered to confer disease protection in these individuals are elusive but important to understand and potentially elicit by vaccination. To address this, we compared CD8+ T cell function induced by HIV-1 immunogens and natural infection using polychromatic flow cytometry. HIV-1-specific CD8+ T cells from all four uninfected immunized and 21 infected subjects secreted IFN-gamma and TNF-alpha. However, CD8+ T cells induced by vaccination and primary infection, but not chronic infection, proliferated to their cognate epitopes. Notably, B27- and B57-restricted CD8+ T cells from nonprogressors exhibited greater expansion than those restricted by other alleles. Hence, CD8+ T cells restricted by certain protective alleles can resist replicative defects, which permits expansion and antiviral effector activities. Our findings suggest that the capacity to maintain CD8+ T cell proliferation, regardless of MHC-restriction, may serve as an important correlate of disease protection in the event of infection following vaccination.
authors.affiliation: Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.forename: Ruth
authors.initials: R
authors.lastname: Baydo
authors.forename: Emilie
authors.initials: E
authors.lastname: Jalbert
authors.forename: Justin
authors.initials: J
authors.lastname: Penn
authors.forename: Sean
authors.initials: S
authors.lastname: Wilson
authors.forename: John P
authors.initials: JP
authors.lastname: McNevin
authors.forename: Matthew D
authors.initials: MD
authors.lastname: McSweyn
authors.forename: Deborah
authors.initials: D
authors.lastname: Lee
authors.forename: Yunda
authors.initials: Y
authors.lastname: Huang
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000328:Adult; D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I