Human allograft-derived T-cell lines: donor class I- and class II-directed cytotoxicity and repertoire stability in sequential biopsies.

In order to characterize directly the T-cell repertoire utilized in human renal allograft rejection, we analyzed 20 long-term T-cell lines established from lymphocytic infiltrates present in renal tissue obtained by needle biopsy from transplant patients with rejection indications. All cell lines are strongly cytotoxic against one or more of the HLA antigens for which the kidney donor and the recipient were mismatched. Traditionally, cytotoxicity in allograft rejection has been attributed to CD8-positive cytotoxic T lymphocytes (CTLs) directed against class I alloantigens. Cell lines described here are mixtures of distinct CD4-antigen-positive and CD8-antigen-positive subpopulations, and exhibit class I- as well as class II-directed killing. Using a cell line that demonstrates class II-directed cytotoxicity and a set of class II deletion mutants as target cells, we show that class II antigens, in particular HLA-DP, can serve as targets in renal allograft rejection. The role of CD4-positive CTLs was shown by analysis of clonal populations or sorted CD8-positive and CD4-positive subpopulations. In several instances we have obtained cell lines from serial biopsies performed on the same patient at distinct time points during an ongoing rejection. Comparisons of the phenotype, function, and specificities allow for speculation regarding T-cell population dynamics within the rejection response.