title: Role of LFA-1 in the activation and trafficking of T cells: implications in the induction of chronic colitis.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana, USA.
authors.forename: Iurii
authors.initials: I
authors.lastname: Koboziev
authors.forename: Fridrik
authors.initials: F
authors.lastname: Karlsson
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Ostanin
authors.forename: Laura
authors.initials: L
authors.lastname: Gray
authors.forename: Melissa
authors.initials: M
authors.lastname: Davidson
authors.forename: Songlin
authors.initials: S
authors.lastname: Zhang
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Grisham
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D003092:Colitis / Q000209:etiology* / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
chemical_list: D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1