Limited T-Cell Repertoire in Renal Allograft and Allogeneic Melanoma Transmitted by the Graft1

Abstract

In a patient with metastatic melanoma transmitted by the renal allograft, HLA serves as an alloantigen per se and is associated with tumor antigens at the same time. The influence of this antigeneic pattern on the Vbeta T-cell repertoire in an allogeneic melanoma, allograft, and peripheral blood mononuclear cells (PBMC) was assessed by polymerase chain reaction. Vbeta13.1 and 19 were found in both the melanoma and the graft. Vbeta14 was detected only in the melanoma and Vbeta6 was detected only in the kidney. PBMC revealed an unrestricted Vbeta pattern. Markers for cytotoxic activity of T cells--granzyme B and perforin--were not expressed during immunosuppressive therapy as clinically reflected in a nonrejecting allograft and in a progressing melanoma. In vitro PBMC proliferated to recombinant interleukin-2, whereas recombinant interferon-gamma did not augment this response. Initiation of immune therapy, in addition to discontinuation of immunosuppression, might support the rejection of the allogeneic tumor by dominant Vbeta T cells.

Skew in T-cell receptor usage and clonal T-cell expansion in patients with chronic rejection of transplanted kidneys

“…Quantitative methods, including monoclonal antibodies (25), PCR (18,26), and a hybridization technique (24), have been used for the analysis of TCR repertoires. Clonality of T cells has been analyzed by Southern blot hybridization (27), CDR3 length analysis (15), and single-strand conformation polymorphism (28).…”