| Absence of both IL-7 and IL-15 severely impairs the development of CD8 T cell response against Toxoplasma gondii. | |
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MedLine Citation:
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PMID: 20520779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CD8(+) T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8(+) T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related gamma-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8(+) T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8(+) T cell response. This impairment is characterized by reduction in CD44 expression, IFN-gamma production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8(+) T cells. Interestingly, the absence of both cytokines did not impair initial CD8(+) T cell generation but affected their survival and differentiation into memory phenotype IL-7Ralpha(hi) cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8(+) T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15(-/-) mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8(+) T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8(+) T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported. |
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Authors:
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Rajarshi Bhadra; Hongbing Guan; Imtiaz A Khan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-05-26 |
Journal Detail:
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Title: PloS one Volume: 5 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2010 |
Date Detail:
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Created Date: 2010-06-03 Completed Date: 2010-09-07 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e10842 Citation Subset: IM |
Affiliation:
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Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC., USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies / pharmacology Bromodeoxyuridine / metabolism CD8-Positive T-Lymphocytes / cytology, drug effects, immunology*, parasitology* Cell Cycle / drug effects Down-Regulation / drug effects Interferon-gamma / immunology Interleukin-15 / deficiency*, metabolism Interleukin-7 / deficiency*, immunology Mice Mice, Knockout Parasites / drug effects, immunology Proto-Oncogene Proteins c-bcl-2 / metabolism Receptors, Interleukin-7 / metabolism Spleen / drug effects, immunology, parasitology Staining and Labeling Toxoplasma / drug effects, immunology* Toxoplasmosis / immunology, parasitology Up-Regulation / drug effects Vaccination |
| Grant Support | |
ID/Acronym/Agency:
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AI33325/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Interleukin-15; 0/Interleukin-7; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Interleukin-7; 59-14-3/Bromodeoxyuridine; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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