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-κB (NF-κB) 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_h2 cells. However, in contrast to CD30, Ox40 was also expressed on T_h1 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.