title: Intestinal epithelial cells modulate CD4 T cell responses via the thymus leukemia antigen.
abstract: 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.
authors: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Danyvid
authors: D
authors: Olivares-Villagómez
authors: Holly M Scott
authors: HM
authors: Algood
authors: Kshipra
authors: K
authors: Singh
authors: Vrajesh V
authors: VV
authors: Parekh
authors: Kaitlyn E
authors: KE
authors: Ryan
authors: M Blanca
authors: MB
authors: Piazuelo
authors: Keith T
authors: KT
authors: Wilson
authors: Luc
authors: L
authors: Van Kaer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology*; D005434:Flow Cytometry; D018928:Immunity, Mucosal / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008562:Membrane Glycoproteins; C028388:thymus-leukemia antigens