Journal
SCIENCE IMMUNOLOGY
Volume 3, Issue 29, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.aao2892
Keywords
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Categories
Funding
- Wellcome Trust (WT) Investigator [103865Z/14/Z]
- Medical Research Council (MRC) [J007439, G1001052]
- European Union Seventh Framework Programme [317040]
- Leukemia and Lymphoma Research [15012]
- Brazilian National Council for Scientific Development [206435/2014-2]
- WT Institutional Strategic Support Fund [105609/Z/14/Z]
- WT [090323/Z/09/Z]
- MRC [MR/L018373/L, MR/P001602/1, MR/M019829/1]
- MRC
- NIH
- Cambridge Biomedical Research Centre
- European Research Council under the European Union's Horizon 2020 Research and Innovation Programme [695551]
- NIH [R01 DA13324]
- National Institute of Child Health and Human Development [R01-HD-41224]
- National Institute on Drug Abuse [U01-DA-036297, R01-DA-12568, K24-AI118591]
- IAVI
- USAID
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- Intramural Research Program of the NIH
- Frederick National Laboratory, Center for Cancer Research
- MRC [G1001052, G0901682, G0601072, MR/L006588/1, MR/P011233/1, MR/J007439/1] Funding Source: UKRI
- Wellcome Trust [100326/Z/12/Z] Funding Source: researchfish
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD041224] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [ZIABC010792] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K24AI118591, U01AI067854, U19AI067854] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [U01DA036297, R01DA013324, R01DA012568] Funding Source: NIH RePORTER
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Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell-mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8(+) T cell survival. To investigate the clinical relevance of these observations, we conducted an extensive immunogenetic analysis of multiple independent cohorts of HIV-1-, hepatitis C virus (HCV)-, and human T cell leukemia virus type 1 (HTLV-1)-infected individuals in conjunction with in vitro assays of T cell survival, analysis of ex vivo KIR expression, and mathematical modeling of host-virus dynamics. Our data suggest that functional engagement of inhibitory KIRs enhances the CD8(+) T cell response against HIV-1, HCV, and HTLV-1 and is a significant determinant of clinical outcome in all three viral infections.
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