Mechanisms of alloimmune tolerance associated with mixed chimerism induced by vascularized bone marrow transplants.
Rat limb allograft recipients represent surgically induced, immediately vascularized bone marrow transplant (VBMT) chimeras. The majority of these chimeras undergo tolerance while a minority develop graft versus host disease (GVHD). T-cell chimerism and associated mechanisms of cellular immune nonresponsiveness were investigated in tolerant VBMT chimeras. A strong correlation (p < 0.01) was observed between the clinical onset of GVHD and levels of donor T-cell chimerism approximating or greater than 50%. However, stable mixed chimerism was associated with tolerance. In conclusion, three major sequential mechanisms of immune nonresponsiveness were elucidated in tolerant VBMT chimeras over time and included development of nonspecific suppressor cells (which potentially represent natural suppressor cells), maturation of antigen-specific suppressor cell circuits, and eventually putative clonal inactivation.
Ramsamooj
Rajen
R
University of California Davis Medical Center, Division of Surgical & Transplant Pathology, Sacramento, CA 95817, USA.
Llull
Ramon
R
Patel
Mayuri P
MP
Beko
Kenneth R
KR
Black
Kirby S
KS
Hewitt
Charles W
CW
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D006614:Hindlimb / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D007108:Immune Tolerance / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*