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

Publication ,  Journal Article
Demers, KR; Makedonas, G; Buggert, M; Eller, MA; Ratcliffe, SJ; Goonetilleke, N; Li, CK; Eller, LA; Rono, K; Maganga, L; Nitayaphan, S ...
Published in: PLoS Pathog
August 2016

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.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

August 2016

Volume

12

Issue

8

Start / End Page

e1005805

Location

United States

Related Subject Headings

  • Virology
  • T-Box Domain Proteins
  • Perforin
  • Middle Aged
  • Male
  • Immunity, Cellular
  • Humans
  • HIV Infections
  • Female
  • Chronic Disease
 

Citation

APA
Chicago
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MLA
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Demers, K. R., Makedonas, G., Buggert, M., Eller, M. A., Ratcliffe, S. J., Goonetilleke, N., … Betts, M. R. (2016). Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection. PLoS Pathog, 12(8), e1005805. https://doi.org/10.1371/journal.ppat.1005805
Demers, Korey R., George Makedonas, Marcus Buggert, Michael A. Eller, Sarah J. Ratcliffe, Nilu Goonetilleke, Chris K. Li, et al. “Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection.PLoS Pathog 12, no. 8 (August 2016): e1005805. https://doi.org/10.1371/journal.ppat.1005805.
Demers KR, Makedonas G, Buggert M, Eller MA, Ratcliffe SJ, Goonetilleke N, et al. Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection. PLoS Pathog. 2016 Aug;12(8):e1005805.
Demers, Korey R., et al. “Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection.PLoS Pathog, vol. 12, no. 8, Aug. 2016, p. e1005805. Pubmed, doi:10.1371/journal.ppat.1005805.
Demers KR, Makedonas G, Buggert M, Eller MA, Ratcliffe SJ, Goonetilleke N, Li CK, Eller LA, Rono K, Maganga L, Nitayaphan S, Kibuuka H, Routy J-P, Slifka MK, Haynes BF, McMichael AJ, Bernard NF, Robb ML, Betts MR. Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection. PLoS Pathog. 2016 Aug;12(8):e1005805.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

August 2016

Volume

12

Issue

8

Start / End Page

e1005805

Location

United States

Related Subject Headings

  • Virology
  • T-Box Domain Proteins
  • Perforin
  • Middle Aged
  • Male
  • Immunity, Cellular
  • Humans
  • HIV Infections
  • Female
  • Chronic Disease