4.8 Article

Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0808242105

Keywords

CD8 alpha alpha; mucosal immunity; colitis; nonclassical MHC; immunoregulation

Funding

  1. National Institutes of Health (NIH) [HL68744]
  2. Vanderbilt University Digestive Diseases Research Center Pilot
  3. NIH [P30 DK058404, P30 A154999, CA009385]
  4. Vanderbilt-Meharry Center for AIDS Research Pilot
  5. Cancer Research Institute
  6. National Multiple Sclerosis Society

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Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8 alpha alpha homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.

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