The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance

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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2016-10, Vol.45 (4), p.831-846
Main Authors: Meli, Alexandre P., Fontés, Ghislaine, Avery, Danielle T., Leddon, Scott A., Tam, Mifong, Elliot, Michael, Ballesteros-Tato, Andre, Miller, Jim, Stevenson, Mary M., Fowell, Deborah J., Tangye, Stuart G., King, Irah L.
Format: Article
Language:English
Subjects:
Animals
Antigens
Cell Differentiation - immunology
Cells, Cultured
Experiments
Germinal Center - immunology
Humans
Immunity, Humoral - immunology
Infections
Lymphatic system
Lymphocyte Activation - immunology
Lymphocyte Function-Associated Antigen-1 - immunology
Lymphocytes
Mice
Mice, Inbred C57BL
Proteins
Proto-Oncogene Proteins c-bcl-6 - immunology
Software
T cell receptors
T-Lymphocytes, Helper-Inducer - immunology
Transcription factors
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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. [Display omitted] •Mouse and human Tfh cells have high expression of LFA-1•Survival of Tfh cells during the germinal center reaction requires LFA-1•LFA-1 is required for Tfh cell development and immunity to helminth infection•Tfh cell differentiation selectively requires Talin-1-dependent integrin activation T follicular helper cell differentiation is required for germinal center formation and long-lived humoral immunity. Meli et al. report that a high-affinity form of the integrin LFA-1 regulates both the development and maintenance of this T cell subset and is critical for generation of protective humoral immunity to intestinal helminth infection.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2016.09.018