The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
HIV Infection of Naturally Occurring and Genetically Reprogrammed Human Regulatory T-cells
Open accessAbstract
A T-cell subset, defined as CD4(+)CD25(hi) (regulatory T-cells [Treg cells]), was recently shown to suppress T-cell activation. We demonstrate that human Treg cells isolated from healthy donors express the HIV-coreceptor CCR5 and are highly susceptible to HIV infection and replication. Because Treg cells are present in very few numbers and are difficult to expand in vitro, we genetically modified conventional human T-cells to generate Treg cells in vitro by ectopic expression of FoxP3, a transcription factor associated with reprogramming T-cells into a Treg subset. Overexpression of FoxP3 in naïve human CD4(+) T-cells recapitulated the hyporesponsiveness and suppressive function of naturally occurring Treg cells. However, FoxP3 was less efficient in reprogramming memory T-cell subset into regulatory cells. In addition, FoxP3-transduced T-cells also became more susceptible to HIV infection. Remarkably, a portion of HIV-positive individuals with a low percentage of CD4(+) and higher levels of activated T-cells have greatly reduced levels of FoxP3(+)CD4(+)CD25(hi) T-cells, suggesting disruption of the Treg cells during HIV infection. Targeting and disruption of the T-cell regulatory system by HIV may contribute to hyperactivation of conventional T-cells, a characteristic of HIV disease progression. Moreover, the ability to reprogram human T-cells into Treg cells in vitro will greatly aid in decoding their mechanism of suppression, their enhanced susceptibility to HIV infection, and the unique markers expressed by this subset.
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Cites
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Cited by
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The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs
Allan, S. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24685 · Cited by 444
A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells
Manel, N., Hogstad, B., Wang, Y., Levy, D. E., Unutmaz, D., & Littman, D. R. (2010) · Nature · doi:10.1038/nature09337 · Cited by 427
Self-citationImmune reconstitution inflammatory syndrome: more answers, more questions
Shelburne, S. A., Montes, M., & Hamill, R. J. (2006) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dki444 · Cited by 286
IPEX syndrome: genetics and treatment options
Ben-Skowronek, I. (2021) · Genes · doi:10.3390/genes12030323 · Cited by 64
Metadata
- Authors
- Oswald-Richter, K., Grill, S. M., Shariat, N., Leelawong, M., Sundrud, M. S., Haas, D. W., & Unutmaz, D.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2004-07-13
- Volume
- 2
- Issue
- 7
- Pages
- e198
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2005227771
- Cited by
- 301
- References
- 77
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- gold
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