Induction of non-MHC-restricted cytotoxicity in a patient with pure red cell aplasia: functional relevance to antigen-specific cytotoxic T cells.

Abstract

A functional analysis of an expanded T-cell subpopulation was studied in a patient with pure red cell aplasia who had no evidence of malignancy. In the time of an aggravation of the anemia, an expanded population of large granular lymphocytes (LGL) with T-cell receptor (TCR) alpha beta +CD3+CD8+ phenotype was noted, which reverted to normal with remission. These T cells displayed a polyclonal pattern in DNA analysis. Functionally, the T cells, with suppressor/cytotoxic phenotype exhibited normal capabilities for transducing the signals of the proliferative response, and of interleukin-2R (IL-2R) expression and IL-2 production via the TCR-CD3 complex structure. While they suppressed erythroid colony formation in vitro, neither non-major histocompatibility complex-restricted cytotoxic activity, cytotoxic T-cell activity, nor suppressive activity for immunoglobulin synthesis by B cells was detected. Pretreatment by anti-CD3 or anti-T-cell receptor antibody generated cytotoxicity for FcR+ target cells in the patient cells, but no such augmentation was found with other monoclonal antibodies of FcR- target cells. These findings indicated that the expanded T cells are functionally relevant to antigen-specific cytotoxic T lymphocytes.