L-selectin is dispensable for T regulatory cell function postallogeneic bone marrow transplantation.
In murine models, the adoptive transfer of CD4(+) /CD25(+) regulatory T cells (T(regs) ) inhibited graft-versus-host disease (GvHD). Previous work has indicated a critical role for the adhesion molecule L-selectin (CD62L) in the function of T(regs) in preventing GvHD. Here we examined the capacity of naive wild-type (WT), CD62L(-/-) and ex vivo expanded CD62L(Lo) T(regs) to inhibit acute GvHD. Surprisingly, we found that CD62L(-/-) T(regs) were potent suppressors of GvHD, whereas CD62L(Lo) T(regs) were unable to inhibit disease despite being functionally competent to suppress allo T cell responses in vitro. Concomitant with improved outcomes, WT and CD62L(-/-) T(regs) significantly reduced liver pathology and systemic pro-inflammatory cytokine production, although CD62L(-/-) T(regs) were less effective in reducing lung pathology. While accumulation of CD62L(-/-) T(regs) in GvHD target organs was equivalent to WT T(regs) , CD62L(-/-) T(regs) did not migrate as well as WT T(regs) to peripheral lymph nodes (PLNs) over the first 2 weeks posttransplantation. This work demonstrated that CD62L was dispensable for T(reg) -mediated protection from GvHD.
Department of Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
M J
MJ
Carlson
L M
LM
Fulton
J M
JM
Coghill
M L
ML
West
J E
JE
Burgents
Y
Y
Wan
A
A
Panoskaltsis-Mortari
T F
TF
Tedder
B R
BR
Blazar
J S
JS
Serody
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D054443:Cell Migration Assays; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019041:L-Selectin / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019707:Receptors, Chemokine / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D019707:Receptors, Chemokine; D019041:L-Selectin