Aberrant tissue localization of fungus-specific CD4(+) T cells in IL-10-deficient mice Journal Article


Authors: Rivera, A.; Collins, N.; Stephan, M. T.; Lipuma, L.; Leiner, I.; Pamer, E. G.
Article Title: Aberrant tissue localization of fungus-specific CD4(+) T cells in IL-10-deficient mice
Abstract: Aspergillus fumigatus, a common environmental fungus, can cause lethal invasive infections in immunocompromised hosts. In immunocompetent individuals, however, inhaled A. fumigatus spores prime CD4(+) T cells and activate immune responses that prevent invasive infection. Calibration of inflammatory responses to levels that prevent fungal invasion without inducing collateral tissue damage is essential for host survival, but the underlying regulatory mechanisms remain undefined. Although IL-10 is a validated regulatory cytokine that suppresses immune responses, and IL-10 deficiency or blockade generally enhances immune responses, we find that A. fumigatus-specific T cell frequencies are markedly reduced in airways of IL-10-deficient mice. T cell priming, proliferation, and survival were unaffected by IL-10 deficiency and did not account for decreased frequencies of A. fumigatus-specific T cells in the airways of IL-10-deficient mice. Instead, IL-10 deficiency results in redistribution of A. fumigatusspecific T cells from infected lungs to the gut, a process that is reversed by antibiotic-mediated depletion of intestinal microbes. Our studies demonstrate that disregulated immune responses in the gut can result in dramatic redistribution of pathogen-specific T cells within the host. Copyright © 2009 by The American Association of Immunologists, Inc.
Keywords: controlled study; antibiotic agent; genetics; nonhuman; lymph nodes; cell proliferation; mouse; animal; mouse mutant; animals; mice; mice, knockout; cell survival; cells, cultured; apoptosis; interleukin 10; animal experiment; animal model; cell motion; pathology; mice, inbred c57bl; transgenic mouse; c57bl mouse; mice, transgenic; immunology; cell culture; tissue distribution; lymph node; cd4+ t lymphocyte; cd4-positive t-lymphocytes; epitope; lung; cell migration; cell movement; intestine flora; microbiology; epitopes, t-lymphocyte; intestine; mycosis; intestines; t lymphocyte activation; lymphocyte depletion; aspergillus fumigatus; aspergillosis; cell transfer; airway; interleukin-10
Journal Title: Journal of Immunology
Volume: 183
Issue: 1
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2009-07-01
Start Page: 631
End Page: 641
Language: English
DOI: 10.4049/jimmunol.0900396
PUBMED: 19542472
PROVIDER: scopus
PMCID: PMC2753290
DOI/URL:
Notes: --- - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus"
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MSK Authors
  1. Eric Pamer
    266 Pamer
  2. Ingrid Leiner
    48 Leiner
  3. Lauren Beth Lipuma
    14 Lipuma