LFA-1 is critical for regulatory T cell homeostasis and function.
Cellular adhesion molecules involved in cell-to-cell mediated suppression by Tregs are not well characterized. We found that the majority of Tregs expressed LFA-1 but most strikingly that the frequency of Tregs in LFA-1(-/-) mice was significantly lower (approximately 50%) in the spleen, lymph nodes, and Peyer's patches compared to wild type controls. The reduction in LFA-1(-/-) Treg cells appears due in part to a reduced capacity of LFA-1(-/-) CD4(+)CD25(-) cells to be induced to become Tregs in the lymph nodes. Importantly, we found that LFA-1(-/-) Tregs fail to suppress T cell responses in vitro and have reduced function in vivo. Treg-mediated suppression does not depend on LFA-1 interactions with ICAM-1 on the surface of responder cells. Our data demonstrate that LFA-1 plays a critical role in regulatory T cell homeostasis and function.
Wohler
Jillian
J
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Bullard
Dan
D
Schoeb
Trent
T
Barnum
Scott
S
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D003092:Colitis / Q000276:immunology / Q000473:pathology; D006706:Homeostasis; D066298:In Vitro Techniques; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D016169:Lymphocyte Function-Associated Antigen-1