Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4(+) T cells, interferon-gamma, and CTLA4
Authors
Markees, Thomas G.Phillips, Nancy E.
Gordon, Ethel J.
Noelle, Randolph J.
Shultz, Leonard D.
Mordes, John P.
Greiner, Dale L.
Rossini, Aldo A.
UMass Chan Affiliations
Department of Medicine, Diabetes DivisionDocument Type
Journal ArticlePublication Date
1998-06-17Keywords
AnimalsAntibodies, Monoclonal
Antigens, CD
Antigens, Differentiation
CD4-Positive T-Lymphocytes
CD40 Ligand
Female
*Graft Survival
*Immunoconjugates
Interferon Type II
Interleukin-4
Male
Membrane Glycoproteins
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Skin Transplantation
Spleen
Thymectomy
Transplantation, Homologous
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and anti-CD154 (anti-CD40-ligand) antibody permits BALB/c islet grafts to survive indefinitely and BALB/c skin grafts to survive for approximately 50 d without further intervention. The protocol induces long-term allograft survival, but the mechanism is unknown. We now report: (a) addition of thymectomy to the protocol permitted skin allografts to survive for > 100 d, suggesting that graft rejection in euthymic mice results from thymic export of alloreactive T cells. (b) Clonal deletion is not the mechanism of underlying long-term graft survival, as recipient thymectomized mice were immunocompetent and harbor alloreactive T cells. (c) Induction of skin allograft acceptance initially depended on the presence of IFN-gamma, CTLA4, and CD4(+) T cells. Addition of anti-CTLA4 or anti-IFN-gamma mAb to the protocol was associated with prompt graft rejection, whereas anti-IL-4 mAb had no effect. The role of IFN-gamma was confirmed using knockout mice. (d) Graft survival was associated with the absence of IFN-gamma in the graft. (e) Long-term graft maintenance required the continued presence of CD4(+) T cells. The results suggest that, with modification, our short-term protocol may yield a procedure for the induction of long-term graft survival without prolonged immunosuppression.Source
J Clin Invest. 1998 Jun 1;101(11):2446-55. Link to article on publisher's siteDOI
10.1172/JCI2703Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38114PubMed ID
9616216Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1172/JCI2703