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- Title
A Nonprogressive Clinical Course in HIV-Infected Individuals Expressing Human Leukocyte Antigen B57/5801 Is Associated with Preserved CD8<sup>+</sup> T Lymphocyte Responsiveness to the HW9 Epitope in Nef.
- Authors
Navis, Marjon; Schellens, Ingrid M. M.; van Swieten, Peter; Borghans, José A. M.; Miedema, Frank; Kootstra, Neeltje A.; van Baarle, Debbie; Schuitemaker, Hanneke
- Abstract
The human leukocyte antigen (HLA) B57 allele and the closely related HLA-B5801 allele are overrepresented among human immunodeficiency virus type 1 (HIV-1)-infected individuals with a long-term nonprogressive clinical course of disease (known as "long-term nonprogressors" [LTNPs]). These alleles are, however, also present among individuals with normal disease progression (known as "progressors"). In a comparison of HLA-B57/5801--expressing progressors and LTNPs, we observed a similar prevalence of escape mutations in 4 Nef epitopes and a similar reactivity of CD8+ T cells against 3 of 4 of these epitopes and their autologous escape variants. However, LTNPs tended to have frequent and preserved CD8+ T cell interferon-γ responses against the wild-type-HW9 Nef epitope, whereas progressors did not maintain a specific CD8+ T cell response. This finding is in line with the findings of a more exhausted phenotype of CD8+T cells in progressors, as is demonstrated by their enhanced level of expression of inhibitory receptor"programmed death 1" (PD-1). The results of the present study suggest that preservation of HW9-specific T cell responses is associated with a more benign clinical course of infection.
- Subjects
HIV infections; HIV; HLA histocompatibility antigens; LYMPHOCYTES; EPITOPES; T cells; INFECTION; ETIOLOGY of diseases; CLINICAL trials
- Publication
Journal of Infectious Diseases, 2008, Vol 197, Issue 6, p871
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/528695