Background: L-selectin (CD62L) and β7 integrins are important for trafficking of naive T cells under steady-state conditions. The objectives of this study were to dissect the requirements for T cell–associated CD62L and β7 integrins during initiation, progression, and regulation of chronic colitis.
Methods: Using the T-cell transfer model, we compared colitogenic potential between T cells lacking one or both of these molecules with wild-type T cells. To assess trafficking of cells to the secondary lymphoid tissue and the gut, we performed co-homing experiments.
Results: Adoptive transfer of wild-type, CD62L−/− or β7−/− single-deficient T cells induced moderate to severe disease with slightly different kinetics. However, transfer of CD62L−/− β7−/− double-deficient (DKO) T cells produced significantly attenuated gut inflammation, which correlated with fewer T cells and reduced levels of proinflammatory cytokines in the colon lamina propria. Our subsequent experiments established that lack of colitogenic potential of these cells was due to inability of DKO T cells to home to the secondary lymphoid tissue. Furthermore, homing of in vitro–generated effector DKO T cells to the inflamed intestine was significantly impaired. Lastly, DKO regulatory T cells were ineffective at suppressing colitis induced by wild-type T cells.
Conclusions: We established that T cells can use either CD62L or β7 integrins to induce chronic colitis, but lack of both abrogates their colitogenic potential. Effector T cells critically rely on β7 integrin during their recruitment to the inflamed intestinal mucosa. Finally, regulation of intestinal inflammation by regulatory T cells requires one or both of these adhesion molecules.
Article first published online 11 September 2013
*Center of Excellence for Arthritis and Rheumatology, Louisiana State University Health Sciences Center, Shreveport, Louisiana;
†Division of Gastroenterology and Hepatology, Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and
‡Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
Reprints: Dmitry V. Ostanin, PhD, Department of Medicine, Center of Excellence for Arthritis and Rheumatology, Louisiana State University Health Sciences Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71130-3932 (e-mail: firstname.lastname@example.org).
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D. V. Ostanin is supported by the CCFA Research Fellowship Grant (#1787) and the Arthritis Center of Excellence at LSU Health Sciences Center, and is supported by the Center of Excellence for Arthritis and Rheumatology funds and CCFA Career Developmental Award #2923. The remaining authors have no conflicts of interest to disclose.
Received May 23, 2013
Accepted August 11, 2013