Preservation of T cell proliferation restricted by protective HLA alleles is critical for immune control of HIV-1 infection.
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.
Horton
Helen
H
Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Frank
Ian
I
Baydo
Ruth
R
Jalbert
Emilie
E
Penn
Justin
J
Wilson
Sean
S
McNevin
John P
JP
McSweyn
Matthew D
MD
Lee
Deborah
D
Huang
Yunda
Y
De Rosa
Stephen C
SC
McElrath
M Juliana
MJ
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
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I