Temporal dynamics of CD8+ T cell effector responses during primary HIV infection.

Journal article

The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection.

Authors: Demers, KR; Makedonas, G; Buggert, M; Eller, MA; Ratcliffe, SJ

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PLoS Pathogens
• Volume: 12
• Issue: 8
• Pages: e1005805
• Publication date: 2016-08-01
• Acceptance date: 2016-07-11
• DOI: 10.1371/journal.ppat.1005805
• EISSN: 1553-7374
• ISSN: 1553-7366
• Pmid: 27486665
• Language: English
• Keywords: Humans; Chronic Disease; Adult; Middle Aged; Female; HIV Infections; Cell Proliferation; Male; CD8-Positive T-Lymphocytes; Immunity, Cellular; Perforin; T-Box Domain Proteins