Rejection of cardiac allografts by T cells expressing a restricted repertoire of T-cell receptor V beta genes.
We have recently shown that T cells infiltrating cardiac allografts early in graft rejection use a limited T-cell receptor (TCR) V beta repertoire. In this study we tested whether this limited repertoire of V beta genes is important for graft rejection. A cell line, AL2-L3, was established from LEW lymphocytes infiltrating ACI heart allografts 2 days after transplantation. This cell line is composed of CD4+ T cells that primarily recognize the class II RTI.B major histocompatibility complex (MHC) molecule expressed by the donor graft. This cell line precipitated acute rejection of donor hearts with a median survival time (MST) of 10.5 days following adoptive transfer to sublethally irradiated LEW recipients. This rate of graft rejection was significantly (P < 0.0007) accelerated when compared with a MST of 60 days for allografts in irradiated control recipients. The AL2-L3-mediated acceleration of graft rejection was donor specific as WF third-party heart allografts were rejected with a delayed tempo (MST = 28.5 days). The V beta repertoire of this cell line was primarily restricted to the expression of V beta 4, 15 and 19 genes. The nucleotide sequence analysis of the beta-chain cDNAs from this cell line demonstrated that the restricted use of the V gene repertoire was not shared with the N, D and J regions. A wide variety of CDR3 loops and J beta genes were used in association with selected V beta genes. These data provide evidence for the role a restricted repertoire of V beta genes plays in cardiac allograft rejection in this model. The restricted usage of the V beta repertoire in an early T-cell response to allografts may provide the opportunity to therapeutically disrupt the rejection reaction by targeting selected T-cell populations for elimination at the time of organ transplantation.
Shirwan
H
H
Transplantation Biology Research Laboratory, National Institute of Transplantation, Los Angeles, CA, USA.
Barwari
L
L
Cramer
D V
DV
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007519:Isoantigens / Q000276:immunology; D008969:Molecular Sequence Data; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D000949:Histocompatibility Antigens Class II; D007135:Immunoglobulin Variable Region; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta