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The Journal of Immunology, 1998, 160: 2180-2187.
Copyright © 1998 by The American Association of Immunologists

Expression of the Costimulatory Receptor CD30 Is Regulated by Both CD28 and Cytokines1

Molly C. Gilfillan*,{dagger}, Patricia J. Noel{dagger}, Eckhard R. Podack, Steven L. Reiner*,{dagger},{ddagger} and Craig B. Thompson2,*,{dagger},{ddagger},§

* Committee on Immunology, {dagger} Gwen Knapp Center for Lupus and Immunology Research, {ddagger} Department of Medicine, and § Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637; and University of Miami School of Medicine, Miami, FL 33136

Costimulation was originally defined and characterized during primary T cell activation. The signaling events that regulate subsequent antigen encounters by T cells are less well defined. In this study we examined the role of CD30 in T cell activation and defined factors that regulate expression of CD30 on T cells. We demonstrate that CD30 expression is restricted to activated T cells and regulated by CD28 signal transduction. In contrast to CD28-expressing TCR Tg cells, CD28-deficient TCR Tg cells did not express CD30 when cultured with peptide and APCs. However, rIL-4 reconstituted CD30 expression on CD28-deficient TCR Tg cells. Blockade of CD28 interactions or depletion of IL-4 inhibited the induction of CD30, suggesting that both CD28 and IL-4 play important roles in the induction of CD30 expression on wild-type cells. However, CD28 signaling did not up-regulate CD30 expression solely through its ability to augment IL-4 production because IL-4-deficient T cells stimulated with anti-CD3 and anti-CD28 expressed CD30. Induction of CD30 in the absence of IL-4 was not due to the IL-4-related cytokine IL-13. CD30, when expressed on an activated T cell, can act as a signal transducing receptor that enhances the proliferation of T cells responding to CD3 crosslinking. Collectively, the data suggest that T cell expression of CD30 is dependent on the presence of CD28 costimulatory signals or exogenous IL-4 during primary T cell activation. Once expressed on the cell surface, CD30 can serve as a positive regulator of mature T cell function.




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