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Positive selection of mC46-expressing CD4+ T cells and maintenance of virus specific immunity in a primate AIDS model.
- Source :
-
Blood . 7/11/2013, Vol. 122 Issue 2, p179-187. 9p. - Publication Year :
- 2013
-
Abstract
- Despite continued progress in the development of novel antiretroviral therapies, it has liecome increasingly evident that drug-based treatments will not lead to a functional or sterilizing cure for HIV+ patients. In 2009, an HIV+ patient was effectively cured of HIV following allogeneic transplantation of hematopoietic stem cells (HSCs) from a CCR5-/-donor. The utility of this approach, however, is severely limited because of the difficulty in finding matched donors. Hence, we studied the potential of HIV-resistant stem cells in the autologous setting in a nonhuman primate AIDS model and incorporated a fusion inhibitor (mC46) as the means for developing infection-resistant cells. Pigtail macaques underwent identical transplants and Simian-Human Immunodeficiency Virus (SHIV) challenge procedures with the only variation between control and mC46 macaques being the inclusion of a fusion-inhibitor expression cassette. Following SHIV challenge, mC46 macaques, but not control macaques, showed a positive selection of gene-modified CD4+ T cells in peripheral blood, gastrointestinal tract, and lymph nodes, accounting for >90% of the total CD4+ T-cell population. mC46 macaques also maintained high frequencies of SHIV-specific, gene-modified CD4+ T cells, an increase in nonmodified CD4+ T cells, enhanced cytotoxic. T lymphocyte function, and antibody responses. These data suggest that HSC protection may be a potential alternative to conventional antiretroviral therapy in patients with HIV/AIDS. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00064971
- Volume :
- 122
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 89333219
- Full Text :
- https://doi.org/10.1182/blood-2013-01-482224