Role of LFA‐1 in the activation and trafficking of T cells: Implications in the induction of chronic colitis

Introduction: We have previously demonstrated that adoptive transfer of naïve CD4+ T cells devoid of lymphocyte function‐associated antigen‐1‐deficient (LFA‐1; CD11a/CD18) into recombination activating gene‐1 (RAG‐1) deficient (RAG−/−) mice fails to induce chronic colitis whereas transfer of wild type (WT) T‐cells induces unrelenting and chronic disease. Methods: The objectives of this study were to assess the role of lymphocyte function‐associated antigen‐1 (LFA‐1) in enteric antigen (EAg)‐induced activation of T cells in vitro and in vivo and to define the importance of this integrin in promoting trafficking of T cells to the mesenteric lymph nodes (MLNs) and colon. Results: We found that EAg‐pulsed dendritic cells (DCs) induced proliferation of LFA‐1‐deficient (CD11a−/−) CD4+ T cells that was very similar to that induced using WT T cells, suggesting that LFA‐1 is not required for activation/proliferation of T cells in vitro. Coculture of WT or CD11a−/− T cells with EAg‐pulsed DCs induced the generation of similar amounts of interferon‐gamma, interleukin (IL)‐4, and IL‐10, whereas IL‐17A production was reduced ≈2‐fold in cocultures with CD11a−/− T cells. Short‐term (20–22 hours) trafficking studies demonstrated that while both WT and CD11a−/− T cells migrated equally well into the spleen, liver, lungs, small intestine, cecum, and colon, trafficking of CD11a−/− T cells to the MLNs was reduced by 50% when compared to WT T cells. When the observation period was extended to 3–7 days posttransfer, we observed ≈2–3‐fold more WT T cells within the MLNs and colon than CD11a−/− T cells, whereas T‐cell proliferation (as measured by CFSE dilution) was comparable in both populations. Conclusions: Taken together, our data suggest that LFA‐1 is not required for EAg‐induced activation of CD4+ T cells in vitro or in vivo but is required for trafficking of T cells to the MLNs and homing of colitogenic effector cells to the colon where they initiate chronic gut inflammation. (Inflamm Bowel Dis 2012;)