Negative and positive co-signaling with anti-BTLA (PJ196) and CTLA4Ig prolongs islet allograft survival.
The novel coinhibitory receptor B and T lymphocyte attenuator (BTLA) has been implicated in the regulation of autoimmune and may potentially play a role in alloimmune responses. An anti-BTLA monoclonal antibody has been reported to prolong fully major histocompatibility complex-mismatched cardiac allograft survival, and we test the hypothesis that anti-BTLA monoclonal antibody PJ196 may synergize with cytotoxic T lymphocyte antigen-4 immunoglobulin (CTLA4Ig) costimulatory blockade in islet transplantation. We investigated the potential of PJ196, and show that it did not deplete BTLA expressing cells, but it caused down-regulation of BTLA on the surface of lymphocytes and accumulation of cells with regulatory phenotype at the graft site, promoting islet allograft acceptance together with CTLA4Ig. The combination of BTLA coinhibitory modulation and CTLA4Ig costimulatory blockade may be an effective adjunctive strategy for inducing long-term allograft survival.
The Surgical Medical Research Institute, Department of Surgery, Faculty of Medicine, The University of Alberta, Edmonton, Alberta, Canada.
Wayne
W
Truong
Jennifer C
JC
Plester
Wayne W
WW
Hancock
Jonathan
J
Kaye
Shaheed
S
Merani
Kenneth M
KM
Murphy
Theresa L
TL
Murphy
Colin C
CC
Anderson
A M James
AM
Shapiro
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D018796:Immunoconjugates / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011971:Receptors, Immunologic / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; C488868:BTLA protein, mouse; D018796:Immunoconjugates; D011971:Receptors, Immunologic; D000069594:Abatacept