Anti-CD45RB and donor-specific spleen cells transfusion inhibition allograft skin rejection mediated by memory T cells.
Donor-reactive memory T (Tm)cells mediate accelerated rejection, which is known as a barrier to the survival of transplanted organs. Selective interference with the anti-CD45RB monoclonal antibody (α-CD45RB) reliably induces donor-specific tolerance. In this study, pre-sensitization to female C57BL/6 mice with the skin of female BLAB/c mice generated a large number of Tm cells and resulted in rapid rejection of the secondly transplanted allografts. α-CD45RB did induce the tolerance to skin allograft primarily transplanted but failed to induce tolerance in the pre-sensitized mice. Donor-specific spleen cell transfusion (DST) alone also failed to induce the tolerance in the pre-sensitized recipients. Interestingly, combination of α-CD45RB with DST inhibited the rejection induced by memory T cells in the pre-sensitized mice. CD25+ T-cell depletion in α-CD45RB combined with DST therapy recipients could prevent skin allograft tolerance from establishing. In addition, adoptive transfer of donor-primed memory T cells into the tolerant recipients markedly broke the established tolerance. Our findings indicate that α-CD45RB and DST can synergistically inhibit the accelerated rejection mediated by memory T cells and induce long-term skin allograft acceptance in mice.
Department of General surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.|The Key Laboratory of stem cell and Cellular therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
You-Qiang
YQ
Jian
Department of General surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.|The Key Laboratory of stem cell and Cellular therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
Jian
J
Ye
The Key Laboratory of stem cell and Cellular therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
Hui
H
Qi
The Key Laboratory of stem cell and Cellular therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
Chun-Yan
CY
Deng
The Key Laboratory of stem cell and Cellular therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.|Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Shao-Ping
SP
Deng
Department of General surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.|The Key Laboratory of stem cell and Cellular therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.|Shenzhen Cell Therapy Public Service Platform, Shenzhen, China.
Fu-Rong
FR
Li
D064591:Allografts / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D007156:Immunologic Memory; D007249:Inflammation / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008212:Lymphocyte Depletion; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014019:Tissue Donors
D053645:Interleukin-2 Receptor alpha Subunit; D017493:Leukocyte Common Antigens