CD2 antigen targeting reduces intragraft expression of mRNA-encoding granzyme B and IL-10 and induces tolerance.
We explored the hypothesis that CD2 antigen-specific therapy would reduce intragraft gene expression and facilitate the emergence of transplantation tolerance. This postulate was tested in a murine pancreatic islet cell allograft model in which a novel mAb directed at the CD2 antigen, RM2-2 anti-CD2 mAb (RM2-2 mAb), was used to regulate CD2 antigen-dependent antiallograft response. Peritransplant administration (day -1, 0, and day + 1 with respect to transplantation) of RM2-2 mAb resulted in significantly longer survival of DBA/2 pancreatic islet cell allografts in the B6AFl recipient compared with untreated recipients. RM2-2 mAb therapy facilitated the induction of antigen-specific tolerance: whereas retransplantation with the original donor strain (DBA/2) islet cell allograft was successful, retransplantation with a third-party donor (SJL) islet cell allograft was not. In vivo administration of RM2-2 mAb therapy resulted in a decrease in the percentage of T cells that coexpressed the CD2 antigen (demonstrated by two-color flow cytometry) and in a decrease in intragraft expression of cytotoxic cell specific granzyme B mRNA and IL-10 mRNA (detected by RT-PCR). Our data, in addition to demonstrating for the first time the efficacy of RM2-2 anti-CD2 mAb, suggest that CD2 antigen is a suitable target for the induction of transplantation tolerance.
Kapur
S
S
Division of Nephrology, Department of Transplantation Medicine and Extracorporeal Therapy, The New York Hospital-Cornell Medical Center, New York 10021, USA.
Khanna
A
A
Sharma
V K
VK
Li
B
B
Suthanthiran
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001483:Base Sequence; D018801:CD2 Antigens / Q000276:immunology*; D000939:Epitopes; D015870:Gene Expression / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D053804:Granzymes; D007108:Immune Tolerance / Q000187:drug effects*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D000939:Epitopes; D012333:RNA, Messenger; D016753:Interleukin-10; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases