Intestinal epithelial cells modulate CD4 T cell responses via the thymus leukemia antigen.

Olivares-Villagómez D, Algood HM, Singh K, Parekh VV, Ryan KE, Piazuelo MB, Wilson KT, Van Kaer L
J Immunol. 2011 187 (8): 4051-60

PMID: 21900182 · PMCID: PMC3186831 · DOI:10.4049/jimmunol.1101052

The intestinal epithelium is comprised of a monolayer of intestinal epithelial cells (IEC), which provide, among other functions, a physical barrier between the high Ag content of the intestinal lumen and the sterile environment beyond the epithelium. IEC express a nonclassical MHC class I molecule known as the thymus leukemia (TL) Ag. TL is known to interact with CD8αα-expressing cells, which are abundant in the intestinal intraepithelial lymphocyte compartment. In this report, we provide evidence indicating that expression of TL by IEC modulates the cytokine profile of CD4(+) T cells favoring IL-17 production. We show in an adoptive transfer model of colitis that donor-derived cells become more pathogenic when TL is expressed on IEC in recipient animals. Moreover, TL(+)IEC promote development of IL-17-mediated responses capable of protecting mice from Citrobacter rodentium infection. We also show that modulation of IL-17-mediated responses by TL(+)IEC is controlled by the expression of CD8α on CD4(+) T cells. Overall, our results provide evidence for an important interaction between IEC and CD4(+) T cells via TL, which modulates mucosal immune responses.

MeSH Terms (16)

Adoptive Transfer Animals CD4-Positive T-Lymphocytes Cell Separation Coculture Techniques Colitis Epithelial Cells Flow Cytometry Immunity, Mucosal Intestinal Mucosa Lymphocyte Activation Membrane Glycoproteins Mice Mice, Inbred C57BL Mice, Knockout Reverse Transcriptase Polymerase Chain Reaction

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