Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: This study addresses the question of the mechanism for maintaining tolerance to donor alloantigen in the absence of antigen and the role of secondary lymphoid tissues. METHODS: Depleting anti-CD4 antibody administration in conjunction with allogeneic heart transplantation generates donor-specific operational tolerance. Primary C57BL/6 heart grafts were transplanted into the neck cavity of the anti-CD4 antibody pretreated C3H/He mice. At day 50, functioning heart grafts were removed from tolerant mice. At day 100, a secondary C57BL/6 or a third-party heart was transplanted into the abdomen. RESULTS: Anti-CD4 antibody therapy induced CD4CD25 regulatory T cells by 50 days after transplantation, as depleting anti-CD25 treatment in tolerant mice abrogated graft prolongation when spleen leukocytes were adoptively transferred to syngeneic mice. Tolerance was maintained by CD4CD25 regulatory T cells via a CTLA-4 signal at 100 days, even after removal of the primary graft at day 50. Administration of anti-CD25 antibody immediately after removal of the primary graft did not break tolerance, as five out of six second allografts transplanted at day 100 were accepted. Anti-CD25 antibody therapy in conjunction with splenectomy, but not thymectomy, immediately after removal of primary heart grafts at day 50 broke tolerance at day 100; all allografts were rejected. CONCLUSION: The spleen is important in maintaining CD4CD25 regulatory T cells after primary allograft removal.

Original publication

DOI

10.1097/01.tp.0000259928.16003.aa

Type

Journal article

Journal

Transplantation

Publication Date

15/05/2007

Volume

83

Pages

1226 - 1233

Keywords

Adoptive Transfer, Animals, Antibodies, Monoclonal, Antigens, CD, Antigens, Differentiation, CTLA-4 Antigen, Cardiac Surgical Procedures, Drug Administration Schedule, Heart Transplantation, Immune Tolerance, Interleukin-2 Receptor alpha Subunit, Isoantigens, Mice, Mice, Inbred Strains, Postoperative Period, Spleen, Splenectomy, T-Lymphocytes, Regulatory, Tissue Donors, Transplantation, Heterotopic, Transplantation, Homologous