| Autor: |
Favre D; Division of Experimental Medicine, University of California at San Francisco, San Francisco, CA, USA., Stoddart CA, Emu B, Hoh R, Martin JN, Hecht FM, Deeks SG, McCune JM |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2011 Feb 17; Vol. 117 (7), pp. 2189-99. Date of Electronic Publication: 2011 Jan 03. |
| DOI: |
10.1182/blood-2010-06-288035 |
| Abstrakt: |
HIV infection can result in depletion of total CD4(+) T cells and naive CD8(+) T cells, and in the generation of dysfunctional effector CD8(+) T cells. In this study, we show that naive CD8(+) T cells in subjects with progressive HIV disease express low levels of CD8α and CD8β chains. Such naive CD8(low) T cells display broad signaling defects across the T-cell receptor complex, and their appearance correlates with generalized up-regulation of major histocompatibility complex class I (MHC-I) antigens on peripheral blood mononuclear cells (PBMCs). To explore a causal link between increased MHC-I up-regulation and the generation of naive CD8(low) T cells, we used the humanized SCID-hu Thy/Liv mouse model to show that HIV infection of the thymus and interferon α (IFNα) treatment alone result in MHC-I up-regulation and in the generation of dysfunctional CD3(high)CD8(+)CD4(-) single-positive 8 (SP8) thymocytes with low expression of CD8. We suggest that dysfunctional naive CD8(low) T cells are generated as a result of IFNα-mediated up-regulation of MHC-I on stromal cells in the thymus and antigen-presenting cells in the periphery, and that dysfunction in this naive compartment contributes to the immunodeficiency of HIV disease. This study is registered at www.clinicaltrials.gov as NCT00187512. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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