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The role of CD30 in the regulation of T cell function

University of British Columbia

CD30 is a member of the TNFR superfamily that was initially identified on Reed-Sternberg cells of Hodgkin's disease and is widely expressed in other lymphomas as well as in a number of autoimmune diseases. On normal cells, CD30 is expressed primarily on activated CD8⁺ T cells and is induced by two distinct pathways, an IL-4 dependent pathway and an IL-4-independent pathway via CD28. The precise role of CD30 has been controversial, but it has been implicated in a number of T cell functions, including costimulation, cytokine production, cell survival and cytotoxicity, although much of the published work to date has been carried out in cell lines. In an attempt to elucidate the role of CD30 in normal T cells, the function of primary lymphocytes derived from CD30-deficient mice was studied. In the absence of CD30, proliferation and activation were normal, with CD30[sup -/-] cells exhibiting levels of proliferation and expression of activation markers comparable to that of wild type cells. As well, among those cytokines examined, production by activated CD30-deficient cells was normal, although production of IL-4 was reduced compared to wild type. 2C-transgenic CD30-deficient cells were unable to kill specific target cells to the same extent as wild type effectors, although expression of effector molecules including perforin, granzyme B and FasL was normal, as was killing of targets when the requirement for TCR recognition was bypassed. Finally, although the reduction of effector function suggested that memory development may also be effected, 2C/CD30[sup -/-] effectors were able to develop into memory-like cells to the same extent as wild type cells. Although the deletion of CD30 has little effect on a number of T cell functions, particularly activation and proliferation, it appears that CD30 does play a role in the regulation of later events such as cytotoxic effector function and the maintenance of IL-4 production.

Thesis/Dissertation

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2009-11-02

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http://hdl.handle.net/2429/14546

Microbiology and Immunology

University of British Columbia

UBCV

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