[PDF][PDF] The integrin LFA-1 controls T follicular helper cell generation and maintenance

AP Meli, G Fontés, DT Avery, SA Leddon, M Tam… - Immunity, 2016 - cell.com
AP Meli, G Fontés, DT Avery, SA Leddon, M Tam, M Elliot, A Ballesteros-Tato, J Miller…
Immunity, 2016cell.com
T follicular helper (Tfh) cells are a CD4+ T cell subset critical for long-lived humoral
immunity. We hypothesized that integrins play a decisive role in Tfh cell biology. Here we
show that Tfh cells expressed a highly active form of leukocyte function-associated antigen-1
(LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-
1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation,
and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral …
Summary
T follicular helper (Tfh) cells are a CD4+ T cell subset critical for long-lived humoral immunity. We hypothesized that integrins play a decisive role in Tfh cell biology. Here we show that Tfh cells expressed a highly active form of leukocyte function-associated antigen-1 (LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation, and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral immunity to intestinal helminth infection. Furthermore, we demonstrated that expression of Talin-1, an adaptor protein that regulates LFA-1 affinity, dictated Tfh versus Th2 effector cell differentiation. Collectively, our results define unique functions for LFA-1 in the Tfh cell effector program and suggest that integrin activity is important in lineage decision-making events in the adaptive immune system.
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