title: A given number of effector T cells can only destroy a limited number of target cells in graft rejection.
abstract: Anti-donor T cells mediate graft rejection and the frequency of anti-donor T cells directly correlates with transplant outcome. It has long been noted that long-term tolerance was occasionally observed in minor mismatched recipients, little is known about the mechanisms underlying this phenomenon. To quantitatively analyze the relationship between anti-donor T cells and target cells, long-term tolerant C57BL/6 mice were established by infusing 3 x 10(7) F1 splenocytes during the neonatal period. The removal of anti-donor T cells in these mice was demonstrated by unresponsiveness in mixed-lymphocyte reaction. A total of 2 x 10(7) or 5 x 10(7) syngenic naive cells were transferred into long-term tolerant mice; the dose of 5 x 10(7) syngenic cells destroyed chimerism and the skin grafts, while the dose of 2 x 10(7) syngenic cells led to loss of chimerism but the survival of the skin grafts. On Day 20 after the transfusion, a portion of 5 x 10(7) syngenic cells still remained in the mice, while no syngenic cells were detected in mice that received a total of 2 x 10(7) syngenic cells suggesting that these cells were completely exhausted. Syngenic CD4+ T cells proliferated and activated in both groups, while syngenic cells in the low-dose group were more susceptible to apoptosis than those in the high-dose group. Our results suggest that a given number of effector T cells could only kill a limited number of target cells. When that limit was reached, the T cells died. This novel concept not only provides a reasonable explanation for long-term tolerance in minor mismatched transplantation but also provides new insight into tolerance induction that depleting alloreactive T cells in recipients by donor cells or agents is a prerequisite for reconstitution of thymus by donor cells, the establishment of central tolerance is the key for successful tolerance induction.
authors.affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Peiguo
authors.initials: P
authors.lastname: Zheng
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.forename: Jiyu
authors.initials: J
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Quan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D016038:Skin Transplantation
chemical_list: D015778:Minor Histocompatibility Antigens