[Experimental study of immunological tolerance induced by cytotoxic T lymphocyte-associated antigen 4 immunoglobulin in fresh bone allografts].
OBJECTIVE
To study the immunological tolerance induced by blocking the second signal of T cell with extrinsic cytotoxic T lymphocyte-associated antigen 4 immuno globulin (CTLA4-Ig).


METHODS
Fifty-four BALB/C mice, inbred strains, were employed as recipients of bone allografts, using a model of heterotopic muscle pouch. The 54 mice were divided into 3 groups and 18 for each group. The first group, in which the donor was C57BL/6 with intraperitoneal injection of L6 (as a control), was named AL group. The second group, also C57BL/6 with injection CTLA4-Ig, was named AC group. The third group, homologous BALB/C with injection of PBS buffer solution, was named AB group. The serum antibody, lymphocyte proliferation of the second stimulation by splenic cell and bone supernatant of donor, the analysis of lymphocyte subsets, a regraft experiment and histology were determined 2, 4 and 6 weeks after transplantation. The second transplantation was to regraft C57BL/6 (BC group) and C3H (BH group) mice respectively after first 12 mice being transplanted with C57BL/6 and injected with CTLA4-Ig as to detect donor-specificity of immunological tolerance.


RESULTS
Compared with AB group, AL group created more intensive immune rejection: CD4 T cell subsets (P<0.05), the serum antibody (P<0.05) and lymphocyte proliferation of the second stimulation by splenic cell and bone supernatant of donor (P<0.01 and 0.05) were significantly increased. However, the results of AC group showed that CTLA4-Ig significantly inhibited the immune rejection: CD4 T cell subsets (P>0.05), the serum antibody (P>0.05), and lymphocyte proliferation of the second stimulation (P>0.05) were similar to those of AB group. Histological observation of AC group showed that lymphocyte infiltration disappeared, cartilage and new bone formed, and bone marrow cavities emerged. A regraft experiment showed that CD4 T cell subsets (P<0.05) and lymphocyte proliferation of the second stimulation by splenic cell and bone supernatant of donor (P<0.05), BC group was significantly lower than those of BH group. So the immunological tolerance induced by CTLA4-Ig was of donor-specificity.


CONCLUSIONS
The immunological tolerance induced by CTLA4-Ig was prolonged for 6 weeks. This study provides a brand-new path for bone transplantation, which can be helpful to other organ transplantation.
Guo
Chuanyou
C
The Orthopedic Department, Ninth People's Hospital of Shanghai Second Medical University, Shanghai, 200011, PR China. gobl@publicl.sta.net.cn
Dai
Kerong
K
Tang
Tingting
T
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000494:pharmacology*; D016025:Bone Transplantation / Q000276:immunology*; D060908:CTLA-4 Antigen; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011897:Random Allocation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D023001:Transplantation Tolerance / Q000187:drug effects* / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse