Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-11235
Rehr, M; Cahenzli, J; Haas, A; Price, D A; Gostick, E; Huber, M; Karrer, U; Oxenius, A (2008). Emergence of polyfunctional CD8+ T cells after prolonged suppression of human immunodeficiency virus replication by antiretroviral therapy. Journal of Virology, 82(7):3391-3404.
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Progressive human immunodeficiency virus type 1 (HIV-1) infection is often associated with high plasma virus load (pVL) and impaired CD8(+) T-cell function; in contrast, CD8(+) T cells remain polyfunctional in long-term nonprogressors. However, it is still unclear whether CD8(+) T-cell dysfunction is the cause or the consequence of high pVLs. Here, we conducted a longitudinal functional and phenotypic analysis of virus-specific CD8(+) T cells in a cohort of patients with chronic HIV-1 infection. During the initiation and maintenance of successful antiretroviral therapy (ART), we assessed whether the level of pVL was associated with the degree of CD8(+) T-cell dysfunction. Under viremic conditions, HIV-specific CD8(+) T cells were dysfunctional with respect to cytokine secretion (gamma interferon, interleukin-2 [IL-2], and tumor necrosis factor alpha), and their phenotype suggested limited potential for proliferation. During ART, cytokine secretion by HIV-specific CD8(+) T cells was gradually restored, IL-7Ralpha and CD28 expression increased dramatically, and PD-1 levels declined. Thus, prolonged ART-induced reduction of viral replication and, hence, presumably antigen exposure in vivo, allows a significant functional restoration of CD8(+) T cells with the appearance of polyfunctional cells. These findings indicate that the level of pVL as a surrogate for antigen load has a dominant influence on the phenotypic and functional profile of virus-specific CD8(+) T cells.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||27 Jan 2009 18:01|
|Last Modified:||05 Apr 2016 12:52|
|Publisher:||American Society for Microbiology|
|Additional Information:||Copyright: American Society for Microbiology|
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