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Specific CD8+ T cell responses correlate with control of simian immunodeficiency virus replication in Mauritian cynomolgus macaques

Budde, Melisa L., Greene, Justin M., Chin, Emily N., Ericsen, Adam J., Scarlotta, Matthew, Cain, Brian T., Pham, Ngoc H., Becker, Ericka A., Harris, Max, Weinfurter, Jason T., O'Connor, Shelby L., Piatak Jr., Michael, Lifson, Jeffrey D., Gostick, Emma, Price, David, Friedrich, Thomas C. and O'Connor, David H. 2012. Specific CD8+ T cell responses correlate with control of simian immunodeficiency virus replication in Mauritian cynomolgus macaques. Journal of Virology 86 (14) , pp. 7596-7604. 10.1128/JVI.00716-12

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Abstract

Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8+ T cells, but it is not clear whether particular CD8+ T cell responses or a broad repertoire of epitope-specific CD8+ T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0022-538X/ (accessed 25/02/2014)
Publisher: American Society for Microbiology
ISSN: 0022-538X
Date of First Compliant Deposit: 30 March 2016
Last Modified: 11 Jun 2019 20:49
URI: http://orca.cf.ac.uk/id/eprint/42339

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