CD18 is required for optimal development and function of CD4+CD25+ T regulatory cells.
CD4+CD25+ T regulatory (Treg) cells inhibit immunopathology and autoimmune disease in vivo. CD4+CD25+ Treg cells' capacity to inhibit conventional T cells in vitro is dependent upon cell-cell contact; however, the cell surface molecules mediating this cell:cell contact have not yet been identified. LFA-1 (CD11a/CD18) is an adhesion molecule that plays an established role in T cell-mediated cell contact and in T cell activation. Although expressed at high levels on murine CD4+CD25+ Treg cells, the role of LFA-1 in these cells has not been defined previously. We hypothesized that LFA-1 may play a role in murine CD4+CD25+ Treg function. To evaluate this, we analyzed LFA-1-deficient (CD18-/-) CD4+CD25+ T cells. We show that CD18-/- mice demonstrate a propensity to autoimmunity. Absence of CD18 led to diminished CD4+CD25+ T cell numbers and affected both thymic and peripheral development of these cells. LFA-1-deficient CD4+CD25+ T cells were deficient in mediating suppression in vitro and in mediating protection from colitis induced by the transfer of CD4+CD25- T cells into lymphopenic hosts. Therefore, we define a crucial role for CD18 in optimal CD4+CD25+ Treg development and function.
Marski
Marissa
M
Department of Medicine, University of Chicago, IL 60637, USA.
Kandula
Sravanthi
S
Turner
Jerrold R
JR
Abraham
Clara
C
D000818:Animals; D015551:Autoimmunity; D018821:CD18 Antigens / Q000235:genetics / Q000502:physiology*; D003092:Colitis / Q000276:immunology; D018655:Lymphocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000502:physiology*
D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D015375:Receptors, Interleukin-2