Transforming growth factor-beta and interleukin-10 subvert alloreactive delayed type hypersensitivity in cardiac allograft acceptor mice.
We have previously reported that temporary treatment of cardiac allograft recipients with gallium nitrate (GN) results in indefinite graft survival, and the inability to mount donor-reactive delayed type hypersensitivity (DTH) responses. We report that antibodies to either transforming growth factor-beta (TGFbeta) or interleukin-10 (IL10) can uncover DTH responses to donor alloantigens in cardiac allograft acceptor mice. The DTH responses uncovered with TGFbeta-reactive antibodies can be blocked by exogenous IL10, and those uncovered with IL10-reactive antibodies can be blocked by exogenous TGFbeta. These data demonstrate that allograft acceptor mice are fully allosensitized, and poised to make donor-reactive cell-mediated immune responses. However, such responses are subverted by a donor alloantigen-dependent mechanism that involves TGFbeta and IL10, which in turn interfere with local cell-mediated immune responses.
Bickerstaff
A A
AA
Department of Surgery, The Ohio State University College of Medicine, Columbus 43210, USA.
VanBuskirk
A M
AM
Wakely
E
E
Orosz
C G
CG
D000818:Animals; D000917:Antibody Formation; D016027:Heart Transplantation / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000502:physiology; D016753:Interleukin-10 / Q000276:immunology* / Q000494:pharmacology; D007518:Isoantibodies / Q000187:drug effects / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology; D014184:Transplantation, Homologous / Q000276:immunology
D007518:Isoantibodies; D007519:Isoantigens; D016212:Transforming Growth Factor beta; D016753:Interleukin-10