T-cell immune response cDNA 7 in allograft rejection and inflammation.
The membrane protein T-cell immune response cDNA 7 (TIRC7) is transiently expressed in subsets of lymphocytes following antigen stimulation. The importance of TIRC7 in immune activation is demonstrated by the effect of antibodies directed against extracellular domains of TIRC7. In vitro targeting of TIRC7 inhibits proliferation and cytokine expression in human, mouse and rat lymphocytes, and these inhibitory effects have been associated with induction of cytotoxic T-lymphocyte antigen 4 mRNA and protein in the presence of TIRC7 antibodies. In vivo, anti-TIRC7 antibodies prevent kidney transplant rejection in rats and heart allograft rejection in mice. Treatment with an anti-TIRC7 antibody as monotherapy or in combination with TNFalpha blockade inhibits disease progression in collagen-induced arthritis. TIRC7 expression decreases in the peripheral blood of humans who have undergone cardiac transplant prior to clinical rejection, and is therefore a promising noninvasive tool for the prediction of rejection. Thus, targeting of TIRC7 may lead to the development of specific and effective therapeutic and diagnostic approaches by unifying relevant cellular and molecular responses in T- and B-cell subsets, and represents a promising new pathway for immune regulation in transplantation and autoimmune disease.
Utku
Nalân
N
GenPat77 AG, Robert Koch Platz 4, Berlin 10117, Germany. utku@genpat77.com
Heinemann
Thomas
T
Milford
Edgar L
EL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014184:Transplantation, Homologous; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007155:Immunologic Factors; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases