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Preservation of T Cell Proliferation Restricted by Protective HLA Alleles Is Critical for Immune Control of HIV-1 Infection

2006; American Association of Immunologists; Volume: 177; Issue: 10 Linguagem: Inglês

10.4049/jimmunol.177.10.7406

1550-6606

Helen Horton, Ian Frank, Ruth Baydo, Emilie Jalbert, Justin L. Penn, Sean Wilson, John McNevin, Matthew D. McSweyn, Deborah Lee, Yunda Huang, Stephen C. De Rosa, M. Juliana McElrath,

T-cell and B-cell Immunology

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-γ and TNF-α. 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.