Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection.

Abstract

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: Korey R Demers, George Makedonas, Marcus Buggert, Michael A Eller, Sarah J Ratcliffe, Nilu Goonetilleke, Chris K Li, Leigh Anne Eller, Kathleen Rono, Lucas Maganga, Sorachai Nitayaphan, Hannah Kibuuka, Jean-Pierre Routy, Mark K Slifka, Barton F Haynes, Andrew J McMichael, Nicole F Bernard, Merlin L Robb, Michael R Betts
• Journal: PLoS pathogens (PLoS Pathog) Vol. 12 Issue 8 Pg. e1005805 (08 2016) ISSN: 1553-7374 [Electronic] United States
• PMID: 27486665 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• T-Box Domain Proteins
• T-box transcription factor TBX21
• Perforin

Topics

• Adult
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Cell Proliferation
• Chronic Disease
• Female
• HIV Infections (immunology, pathology)
• Humans
• Immunity, Cellular
• Male
• Middle Aged
• Perforin (immunology)
• T-Box Domain Proteins (immunology)