J Korean Soc Transplant.  2005 Dec;19(2):119-123.

Alteration of Molecules and Cytokines Related to the Activation of T Lymphocyte in Immune Tolerance Induced Mice Model

• Hur SM
• Kwon CH
• Joh JW
• Kim SJ

Abstract

PURPOSE
Monoclonal antibodies (mAb) specific for CD45RB as a potent tolerogenic target can prolong allograft survival in several animal models. The mechanisms of CD45RB mAb-mediated tolerance are largely unknown. Therefore, the present studies were performed to determine the immunomodulatory effects of CD45RB mAb on T cells in early or late time after allogenic skin transplantation.
METHODS
Skin grafts and bone marrows from BALB/c donor mice were transplanted on C57BL/6 recipient mice and Busulfan was administerd. Group 1 was composed of anti-CD154 mAb administerd mice, group 2 was composed of anti-CD154 and anti-CD45RBB mAb administerd mice, and group 3 consisted of anti-CD154 mAb and CTLA4-Ig administerd mice. The proportion of splenic CD4+ and CD8+ T cell and range of CD45RB was observed by flow cytometry. Cytokines secreted by CD4+ T cell were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS
CD45RB mAb in combination with CD154 mAb enhanced graft survival in allogenic skin transplantation model where CD45RB mAb specific for CD45RB, which was proven mainly expressed by CD8+ T cells, had inhibitory effects on the proportion of splenocyte-derived CD8+ and CD4+CD45RB(high) T cells in early or late time posttransplant.
CONCLUSION
The combined therapy showed decreases in the proliferation of CD8+ T cells in vivo and allospecific responses of IFN-gamma-producing cells. Such immunomodulatory effects may be associated with the tolerogenic ability of CD45RB mAb in allogenic skin transplantation.

Keyword

CD45RB; Monoclonal antibody; T cell; Allogenic skin transplantation

MeSH Terms

Abatacept
Allografts
Animals
Antibodies, Monoclonal
Bone Marrow
Busulfan
Cytokines*
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Graft Survival
Humans
Immune Tolerance*
Lymphocytes*
Mice*
Models, Animal
Skin
Skin Transplantation
T-Lymphocytes
Tissue Donors
Transplants
Antibodies, Monoclonal
Busulfan
Cytokines