Alloreactive T cell responses and acute rejection of single class II MHC-disparate heart allografts are under strict regulation by CD4+ CD25+ T cells.
Skin but not vascularized cardiac allografts from B6.H-2bm12 mice are acutely rejected by C57BL/6 recipients in response to the single class II MHC disparity. The underlying mechanisms preventing acute rejection of B6.H-2bm12 heart allografts by C57BL/6 recipients were investigated. B6.H-2bm12 heart allografts induced low levels of alloreactive effector T cell priming in C57BL/6 recipients, and this priming was accompanied by low-level cellular infiltration into the allograft that quickly resolved. Recipients with long-term-surviving heart allografts were unable to reject B6.H-2bm12 skin allografts, suggesting potential down-regulatory mechanisms induced by the cardiac allografts. Depletion of CD25+ cells from C57BL/6 recipients resulted in 15-fold increases in alloreactive T cell priming and in acute rejection of B6.H-2bm12 heart grafts. Similarly, reconstitution of B6.Rag(-/-) recipients with wild-type C57BL/6 splenocytes resulted in acute rejection of B6.H-2bm12 heart grafts only if CD25+ cells were depleted. These results indicate that acute rejection of single class II MHC-disparate B6.H-2bm12 heart allografts by C57BL/6 recipients is inhibited by the emergence of CD25+ regulatory cells that restrict the clonal expansion of alloreactive T cells.
Schenk
Soren
S
Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Kish
Danielle D
DD
He
Chunshui
C
El-Sawy
Tarek
T
Chiffoleau
Eise
E
Chen
Chuangqi
C
Chen
Chuangqui
C
Wu
Zihao
Z
Sandner
Sigrid
S
Gorbachev
Anton V
AV
Fukamachi
Kiyotaka
K
Heeger
Peter S
PS
Sayegh
Mohamed H
MH
Turka
Laurence A
LA
Fairchild
Robert L
RL
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
D000949:Histocompatibility Antigens Class II; D015375:Receptors, Interleukin-2