CD30 EXPRESSION IDENTIFIES A FUNCTIONAL ALLOREACTIVE HUMAN T-LYMPHOCYTE SUBSET1

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Abstract
CD30 is a member of the tumor necrosis factor/nerve growth factor receptor family and has been proposed as a marker of specific cytokine-producing subsets in humans. Previous studies have examined the expression of CD30 on established T helper type 1 and T helper type 2 cell clones and the function of CD30+cells after mitogenic stimulation. In this study, we examined the development and function of CD30+T cells generated in response to alloantigen. Primary one-way mixed lymphocyte reactions were established, and the expression of CD30 on T lymphocytes was determined by immunofluorescence and flow cytometry. Fluorescence-activated cell sorting was utilized to define the cytokine profile of alloactivated CD30+cells after restimulation with anti-CD3 monoclonal antibodies or alloantigen. The effect of cyclosporine on the development of CD30+cells, and on cytokines produced by CD30+T lymphocytes, in response to alloantigen was determined. CD30+T lymphocytes could be detected on day 2 of mixed lymphocyte reactions and continued to increase in number and proportion through day 6. Both CD4 and CD8 T cells expressed CD30 after primary alloantigenic stimulation. CD30+T cells are a subset of alloactivated T cells and are the major source of interferon-γ and interleukin-5 produced in response to alloantigen. Cyclosporine partially, but not completely, inhibits the development of CD30+cells, and has a greater effect on interferon-γ production than on interleukin-5 production. CD30+T lymphocytes may constitute an important immunoregulatory subset in human allograft rejection.