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

Abstract

The objectives of this study were to assess the role of 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 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. Co-culture of WT or CD11a−/− T-cells with EAg-pulsed DCs induced the generation of similar amounts of INF-γ, IL-4 and IL-10 whereas IL-17A production was reduced approximately 2-fold in co-cultures with CD11a−/− T-cells. Short term (20-22 hr) 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 from 3-7 days post transfer, we observed approximately 2-3 fold more WT T-cells within the MLNs and colon than CD11a−/− T-cells whereas T cell proliferation (as measured by CSFE 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.

The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment

“…Here, Wang and coworkers demonstrated that the TGF-ß secretion of Treg required the expression of CD18 [ 206 ] and that LFA-1 is essential for an effective inhibition of T cell proliferation [ 207 ]. In accordance with these findings, the importance of LFA-1, expressed on T cells, for the induction of tolerance and the suppression of inflammation has been documented in various autoimmune diseases, such as experimental autoimmune encephalitis (EAE) [ 208 , 209 ], systemic sclerosis [ 210 , 211 ], rheumatoid arthritis, psoriasis [ 193 , 212 ], or systemic lupus erythematosus [ 213 , 214 ]. Notably, in most of these diseases, expression levels of CD11a on T cells inversely correlated with the severity of the disease [ 213 , 215 , 216 ].…”

The transcription factor Mef2d regulates B:T synapse–dependent GC-T FH differentiation and IL-21–mediated humoral immunity

“…S6B), indicating that Mef2d inhibits CD4 T cells from establishing antigen-specific B:T synapse. We assessed expression of Vα2, the TCR α chain of the OTII TCRtg CD4 T cells ( 51 ), and CD18 (β 2 integrin subunit of LFA-1), the lack of which compromises LFA-1 function in CD4 T cells ( 52 ). Expression of both Vα2 and CD18 was comparable between Mef2d-RV and control OTII CD4 T cells (fig.…”

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

“…CD11a −/− mice presented with a reduced frequency of immuno-suppressive Treg fraction in the CNS, which resulted in more severe EAE after immunization [258]. Likewise, CD18 expression was found to be necessary for Treg induction [259,260]. Thus, on one hand transfer of encephalogeneic WT T cells to CD11a −/− mice-lacking Treg-caused a fatal course of the EAE [261].…”