Journal article
Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection
Blood, v 117(18), pp 4805-4815
05 May 2011
PMID: 21398582
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection
- Creators
- Takuya Yamamoto - Immunology Laboratory andDavid A. Price - Cardiff UniversityJoseph P. Casazza - Immunology Laboratory andGuido Ferrari - Duke UniversityMartha Nason - National Institute of Allergy and Infectious DiseasesPratip K. Chattopadhyay - National Institutes of HealthMario Roederer - National Institutes of HealthEmma Gostick - Cardiff UniversityPeter D. Katsikis - Drexel UniversityDaniel C. Douek - National Institutes of HealthRichard Haubrich - University of California San DiegoConstantinos Petrovas - Immunology Laboratory andRichard A. Koup - Immunology Laboratory and
- Publication Details
- Blood, v 117(18), pp 4805-4815
- Publisher
- American Society of Hematology
- Grant note
- K24 AI64086 / National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000290275700022
- Scopus ID
- 2-s2.0-79955955402
- Other Identifier
- 991019339564904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Hematology