CD4+ T cells are sufficient to elicit allograft rejection and major histocompatibility complex class I molecule is required to induce recurrent autoimmune diabetes after pancreas transplantation in mice.
BACKGROUND
We characterized the role of T cell subsets and major histocompatibility complex molecules in allograft rejection and recurrence of autoimmune diabetes.


METHODS
Adoptive cell transfer and vascularized segmental pancreas transplantation were performed in mice.


RESULTS
In an alloimmune response model, transfer of nondiabetic CD4, but not CD8 T cells, elicited pancreas allograft rejection in streptozotocin (STZ)-induced diabetic NOD/scid mice. Pancreas allografts were acutely rejected in STZ-induced diabetic NOD/beta2m mice (confirmed the absence of major histocompatibility complex [MHC] class I and CD8 T cells) and permanently accepted in NOD/CIIT mice (confirmed the absence of MHC class II and CD4 T cells). The results suggest that rejection of pancreas allograft is CD4-dependent and MHC class I-independent. In the autoimmune diabetes model, whole spleen cells obtained from diabetic NOD mice induced autoimmune diabetes in NOD/scid and NOD/CIIT mice, but the onset of diabetes was delayed in NOD/beta2m mice. However, the purified diabetic T cells failed to elicit autoimmune diabetes in NOD/beta2m mice. NOD/scid and NOD/CIIT pancreas grafts were acutely destroyed whereas four of six NOD/beta2m pancreas grafts were permanently accepted in autoimmune diabetic NOD mice.


CONCLUSIONS
CD4 T cells are sufficient for the induction of allograft rejection, and MHC class I molecule is required to induce recurrent autoimmune diabetes after pancreas transplantation in mice.
Xiang
Zhidan
Z
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Ma
Lian-Li
LL
Manicassamy
Santhakumar
S
Ganesh
Balaji B
BB
Williams
Phillip
P
Chari
Ravi
R
Chong
Anita
A
Yin
Deng-Ping
DP
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D006084:Graft Rejection / Q000209:etiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016035:Pancreas Transplantation / Q000009:adverse effects*; D012008:Recurrence; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I