TY - JOUR
T1 - Role of LFA-1 in the activation and trafficking of T cells
T2 - Implications in the induction of chronic colitis
AU - Koboziev, Iurii
AU - Karlsson, Fridrik
AU - Ostanin, Dmitry V.
AU - Gray, Laura
AU - Davidson, Melissa
AU - Zhang, Songlin
AU - Grisham, Matthew B.
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - T cell proliferation
KW - dendritic cells
KW - endothelial cells
KW - enteric antigens
KW - inflammatory bowel disease
KW - leukocyte homing
UR - http://www.scopus.com/inward/record.url?scp=84869210823&partnerID=8YFLogxK
U2 - 10.1002/ibd.22947
DO - 10.1002/ibd.22947
M3 - Article
C2 - 22488891
AN - SCOPUS:84869210823
VL - 18
SP - 2360
EP - 2370
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
SN - 1078-0998
IS - 12
ER -