Supported by a grant from the National Institutes of Health (NIH) (PO1-DK43785; Project 1, Core B (Animal Models Core) and Core C (Histopathology Core).
Role of LFA-1 in the activation and trafficking of T cells: Implications in the induction of chronic colitis†
Article first published online: 5 APR 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 12, pages 2360–2370, December 2012
How to Cite
Koboziev, I., Karlsson, F., Ostanin, D. V., Gray, L., Davidson, M., Zhang, S. and Grisham, M. B. (2012), Role of LFA-1 in the activation and trafficking of T cells: Implications in the induction of chronic colitis. Inflamm Bowel Dis, 18: 2360–2370. doi: 10.1002/ibd.22947
- Issue published online: 15 NOV 2012
- Article first published online: 5 APR 2012
- Manuscript Accepted: 21 FEB 2012
- Manuscript Received: 2 FEB 2012
- endothelial cells;
- dendritic cells;
- enteric antigens;
- inflammatory bowel disease;
- leukocyte homing;
- T cell proliferation
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.
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.
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.
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;)