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An Antibody Combination That Targets Activated T Cells Extends Graft Survival in Sensitized Recipients
Author(s) -
Greenlaw R. E.,
Gardner N. J.,
Farrar C. A.,
Shariff H.,
Sacks S. H.,
Yagita H.,
Simpson E.,
Jurcevic S.
Publication year - 2008
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2008.02393.x
Subject(s) - medicine , immunology , antibody , cd8 , cytotoxic t cell , immune system , antigen , acquired immune system , immunity , biology , in vitro , biochemistry
Memory T cells are the very essence of adaptive immunity with their rapid and efficient response to antigen rechallenge and long‐term persistence. However, it is becoming increasingly evident that when primed with self or transplanted tissue, these cells play a key role in causing and perpetuating tissue damage. Furthermore, current treatments, which efficiently control the naive response, have limited effects on primed T cells. We have used a treatment based on a combination of antibodies specific for molecules expressed by activated T lymphocytes to selectively remove these cells. This approach, which we termed multi‐hit therapy, leads to cumulative binding of antibodies to the target T cells and a striking prolongation of skin graft survival in presensitized recipients in a stringent skin transplant model. The findings are consistent with the depletion of graft‐specific CD4+ and CD8+ T cells, although other modes of action, such as T‐cell regulation and altered migration could play a role. In conclusion, our therapeutic strategy controls primed T cells which are a major driving force in the pathology of many autoimmune diseases and in transplant rejection.