Expression of CD30 and Ox40 on T lymphocyte subsets is controlled by distinct regulatory mechanisms

Members of the TNF receptor (TNFR) superfamily are cell-surface proteins that can be found on most cell types including lymphocytes. Although some TNFR-related molecules are constitutively expressed, others, such as CD30 and Ox40, are induced upon activation of lymphocytes. CD30 and Ox40 are predominantly expressed on activated T helper (T(h))2 cells. Both receptors can activate c-Jun N-terminal kinase (JNK) and nuclear factor-kappaB (NF-kappaB) and have been suggested to play costimulatory roles in lymphocyte activation. To gain further insight into events triggered by both TNFR-related molecules, a detailed analysis of their expression patterns has been performed. We found that CD30 and Ox40 were coexpressed on T(h)2 cells. However, in contrast to CD30, Ox40 was also expressed on T(h)1 cells. Although expression of both receptors is augmented by interleukin-4, only CD30 expression is dependent on signal transducer and activator of transcription (STAT)-6-mediated signaling. Differences in the regulatory pathways controlling expression of CD30 and Ox40 suggest distinct, functional effects triggered by the two TNFR-related molecules during lymphocyte activation.