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Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection.

Publication ,  Journal Article
Yamamoto, T; Price, DA; Casazza, JP; Ferrari, G; Nason, M; Chattopadhyay, PK; Roederer, M; Gostick, E; Katsikis, PD; Douek, DC; Haubrich, R ...
Published in: Blood
May 5, 2011

A highly complex network of coinhibitory and costimulatory receptors regulates the outcome of virus-specific CD8(+) T-cell responses. Here, we report on the expression patterns of multiple inhibitory receptors on HIV-specific, cytomegalovirus-specific, and bulk CD8(+) T-cell memory populations. In contrast to cytomegalovirus-specific CD8(+) T cells, the majority of HIV-specific CD8(+) T cells exhibited an immature phenotype and expressed Programmed Death-1, CD160 and 2B4 but not lymphocyte activation gene-3. Notably, before antiretroviral therapy, simultaneous expression of these negative regulators correlated strongly with both HIV load and impaired cytokine production. Suppression of HIV replication by antiretroviral therapy was associated with reduced surface expression of inhibitory molecules on HIV-specific CD8(+) T cells. Furthermore, in vitro manipulation of Programmed Death-1 and 2B4 inhibitory pathways increased the proliferative capacity of HIV-specific CD8(+) T cells. Thus, multiple coinhibitory receptors can affect the development of HIV-specific CD8(+) T-cell responses and, by extension, represent potential targets for new immune-based interventions in HIV-infected persons.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

May 5, 2011

Volume

117

Issue

18

Start / End Page

4805 / 4815

Location

United States

Related Subject Headings

  • Viremia
  • T-Lymphocyte Subsets
  • Signaling Lymphocytic Activation Molecule Family
  • Receptors, Immunologic
  • Programmed Cell Death 1 Receptor
  • Male
  • Lymphocyte Activation Gene 3 Protein
  • Immunology
  • Immunologic Memory
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yamamoto, T., Price, D. A., Casazza, J. P., Ferrari, G., Nason, M., Chattopadhyay, P. K., … Koup, R. A. (2011). Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood, 117(18), 4805–4815. https://doi.org/10.1182/blood-2010-11-317297
Yamamoto, Takuya, David A. Price, Joseph P. Casazza, Guido Ferrari, Martha Nason, Pratip K. Chattopadhyay, Mario Roederer, et al. “Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection.Blood 117, no. 18 (May 5, 2011): 4805–15. https://doi.org/10.1182/blood-2010-11-317297.
Yamamoto T, Price DA, Casazza JP, Ferrari G, Nason M, Chattopadhyay PK, et al. Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood. 2011 May 5;117(18):4805–15.
Yamamoto, Takuya, et al. “Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection.Blood, vol. 117, no. 18, May 2011, pp. 4805–15. Pubmed, doi:10.1182/blood-2010-11-317297.
Yamamoto T, Price DA, Casazza JP, Ferrari G, Nason M, Chattopadhyay PK, Roederer M, Gostick E, Katsikis PD, Douek DC, Haubrich R, Petrovas C, Koup RA. Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood. 2011 May 5;117(18):4805–4815.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

May 5, 2011

Volume

117

Issue

18

Start / End Page

4805 / 4815

Location

United States

Related Subject Headings

  • Viremia
  • T-Lymphocyte Subsets
  • Signaling Lymphocytic Activation Molecule Family
  • Receptors, Immunologic
  • Programmed Cell Death 1 Receptor
  • Male
  • Lymphocyte Activation Gene 3 Protein
  • Immunology
  • Immunologic Memory
  • Humans