A CD8+/CD103high T cell subset regulates TNF-mediated chronic murine ileitis.
Recruitment of lymphocytes to sites of inflammation requires the sequential engagement of adhesion molecules and chemokine receptors. Of these, the lectin-like molecule CD44 has been particularly implicated in inflammatory trafficking. Using a TNF-driven model of chronic ileitis (i.e., B6.129P-Tnf(Delta)(ARE) mice) that recapitulates many features of Crohn's disease, we demonstrate dynamic changes in the expression and functional state of CD44 on CD8+ T cells. These cells coexpress CD44 and L-selectin, giving them a surface phenotype similar to that of central memory T cells. Yet functionally they exhibit the phenotype of effector T cells, because they produce IFN-gamma. Unexpectedly, depletion of the CD8+ population had no effect on the severity of ileitis. Further analyses showed a second CD8+ population that lacked CD44, but expressed CD103, produced TGF-beta, inhibited the proliferation of CD4+ in vitro, and attenuated adoptively transferred ileitis in vivo, most likely counteracting the proinflammatory role of the CD44(high) subset. Collectively, these data suggest that the presence or absence of CD44 and CD103 on the CD8+ lymphocyte surface defines functionally distinct subsets of CD8+ T cells in vivo. These inflammation-driven populations exert distinct roles during the development of chronic ileitis, and influence the balance of effector and regulatory functions in the chronically inflamed small intestine.
Ho
Johnson
J
Digestive Health Center of Excellence, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Kurtz
Courtney C
CC
Naganuma
Makoto
M
Ernst
Peter B
PB
Cominelli
Fabio
F
Rivera-Nieves
Jesús
J
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002908:Chronic Disease; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D007079:Ileitis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D039001:Integrin alpha Chains / Q000096:biosynthesis*; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D018960:Hyaluronan Receptors; D018836:Inflammation Mediators; D039001:Integrin alpha Chains; D008024:Ligands; D014409:Tumor Necrosis Factor-alpha; C091367:alpha E integrins; D006820:Hyaluronic Acid