title: An antibody combination that targets activated T cells extends graft survival in sensitized recipients.
abstract: 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.
authors.affiliation: Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Greenlaw
authors.forename: N J
authors.initials: NJ
authors.lastname: Gardner
authors.forename: C A
authors.initials: CA
authors.lastname: Farrar
authors.forename: H
authors.initials: H
authors.lastname: Shariff
authors.forename: S H
authors.initials: SH
authors.lastname: Sacks
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: E
authors.initials: E
authors.lastname: Simpson
authors.forename: S
authors.initials: S
authors.lastname: Jurcevic
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D005260:Female; D006085:Graft Survival; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism*