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Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8(+) T Cell Response against Toxoplasma gondii

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...

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Autores principales: Bhadra, Rajarshi, Guan, Hongbing, Khan, Imtiaz A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877110/
https://www.ncbi.nlm.nih.gov/pubmed/20520779
http://dx.doi.org/10.1371/journal.pone.0010842
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author Bhadra, Rajarshi
Guan, Hongbing
Khan, Imtiaz A.
author_facet Bhadra, Rajarshi
Guan, Hongbing
Khan, Imtiaz A.
author_sort Bhadra, Rajarshi
collection PubMed
description 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 γ-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-γ 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-7Rα(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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spelling pubmed-28771102010-06-02 Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8(+) T Cell Response against Toxoplasma gondii Bhadra, Rajarshi Guan, Hongbing Khan, Imtiaz A. PLoS One Research Article 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 γ-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-γ 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-7Rα(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. Public Library of Science 2010-05-26 /pmc/articles/PMC2877110/ /pubmed/20520779 http://dx.doi.org/10.1371/journal.pone.0010842 Text en Bhadra et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bhadra, Rajarshi
Guan, Hongbing
Khan, Imtiaz A.
Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8(+) T Cell Response against Toxoplasma gondii
title Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8(+) T Cell Response against Toxoplasma gondii
title_full Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8(+) T Cell Response against Toxoplasma gondii
title_fullStr Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8(+) T Cell Response against Toxoplasma gondii
title_full_unstemmed Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8(+) T Cell Response against Toxoplasma gondii
title_short Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8(+) T Cell Response against Toxoplasma gondii
title_sort absence of both il-7 and il-15 severely impairs the development of cd8(+) t cell response against toxoplasma gondii
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877110/
https://www.ncbi.nlm.nih.gov/pubmed/20520779
http://dx.doi.org/10.1371/journal.pone.0010842
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