Allograft rejection by T cell receptor transgenic mice.
We have used a line of T cell receptor (TcR) transgenic mice, in which a significant portion of CD8+ T cells expresses a TcR that is specific for the minor histocompatibility antigen H-Y presented by the H-2Db Class I molecule, to examine the immune response to H-Y-incompatible skin or pancreatic islet allografts. Our results indicate that, in contrast to the conclusions of previous reports, pancreatic islet endocrine cells are invulnerable or only weakly vulnerable to an H-Y-directed immune response. An even more unexpected finding was that unlike normal female mice of the C57BL/6 background which consistently reject male skin within a few weeks, TcR transgene+ littermates reject male skin only infrequently. Our results are consistent with the conclusion that the inability of H-Y TcR females to reject male skin is due to a deficiency of cells with male-specific helper activity. Long-term acceptance of male grafts by H-Y TcR females leads to a state of T cell hyporesponsiveness to male skin grafts. In addition, T cells harvested from long-term skin acceptors were hyporesponsive to in vitro stimulation by a clonotype-specific monoclonal antibody. Transgenic mice with TcRs having antigenic specificity for defined transplantation antigens provide a unique model for study of the allograft response.
Bassiri
H
H
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia 19104.
Markmann
J F
JF
Desai
N M
NM
Kim
J I
JI
Teh
H S
HS
Barker
C F
CF
D000818:Animals; D005260:Female; D006084:Graft Rejection; D006182:H-Y Antigen / Q000276:immunology*; D007108:Immune Tolerance; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000502:physiology; D016038:Skin Transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D014184:Transplantation, Homologous
D006182:H-Y Antigen; D011948:Receptors, Antigen, T-Cell