Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD.
CD4+CD25+ regulatory T (Treg) cells are potent modulators of alloimmune responses. In murine models of allogeneic bone marrow transplantation, adoptive transfer of donor CD4+CD25+ Treg cells protects recipient mice from lethal acute graft-versus-host disease (aGVHD) induced by donor CD4+CD25- T cells. Here we examined the differential effect of CD62L+ and CD62L- subsets of CD4+CD25+ Treg cells on aGVHD-related mortality. Both subpopulations showed the characteristic features of CD4+CD25+ Treg cells in vitro and did not induce aGVHD in vivo. However, in cotransfer with donor CD4+CD25- T cells, only the CD62L+ subset of CD4+CD25+ Treg cells prevented severe tissue damage to the colon and protected recipients from lethal aGVHD. Early after transplantation, a higher number of donor-type Treg cells accumulated in host mesenteric lymph node (LN) and spleen when CD4+CD25+CD62L+ Treg cells were transferred compared with the CD62L- subset. Subsequently, CD4+CD25+CD62L+ Treg cells showed a significantly higher capacity than their CD62L- counterpart to inhibit the expansion of donor CD4+CD25- T cells. The ability of Treg cells to efficiently enter the priming sites of pathogenic allo-reactive T cells appears to be a prerequisite for their protective function in aGVHD.
Ermann
Joerg
J
Division of Immunology and Rheumatology, the Department of Medicine, Stanford University School of Medicine, CCSR Bldg, Rm 2215-C, 300 Pasteur Dr, Stanford, CA 94305-5166, USA.
Hoffmann
Petra
P
Edinger
Matthias
M
Dutt
Suparna
S
Blankenberg
Francis G
FG
Higgins
John P
JP
Negrin
Robert S
RS
Fathman
C Garrison
CG
Strober
Samuel
S
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology* / Q000637:transplantation; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006648:Histocompatibility; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive / Q000379:methods*; D019041:L-Selectin; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology*
D015703:Antigens, CD; D015375:Receptors, Interleukin-2; D019041:L-Selectin