CD30 is a lymphoid activation Ag expressed by activated B and T lymphocytes, as well as selected lymphoid malignancies. In T cells, CD30 expression is limited to a minority (15 to 25%) of activated CD45RO+ T cells. Studies were undertaken to define unique functional properties of CD30+ T cells by identifying the profile of cytokine production by CD30+ T cells, and by assessing their ability to provide help for B cell Ig production. Assessment of cytokine mRNA transcripts by reverse transcription-PCR (RT-PCR) revealed the presence of IFN-gamma mRNA transcripts only in CD30+ T cells derived from FACS purified from activated CD45RO+ T cells. IFN-gamma mRNA was present neither in the CD30- subset of activated CD45RO+ T cells, nor in activated CD45RA+ T cells. Both CD30+ and CD30- subsets expressed IL-10 and IL-2R alpha mRNAs after 3 days of activation, but neither population expressed IL-4 or IL-6 transcripts at this time. Furthermore, production of secreted IFN-gamma was significantly greater in activated CD30+CD45RO+ cells (564 +/- 250 pg/ml) than in CD30-CD45RO+ (50 +/- 33 pg/ml) or CD45RA+ (0 +/- 0) T cells. CD30+ T cells also expressed IL-5 mRNA and secreted significantly higher levels of IL-5 (320 +/- 73) than activated CD30-CD45RO+ (17 +/- 5) T cells. In contrast, CD30- T cells produced significantly higher levels of IL-2 than CD30+ T cells (1270 +/- 380 vs 450 +/- 128). Induction of IFN-gamma in CD30+ T cells was not a result of CD30 engagement by Abs used during the isolation process, although an anti-CD30 Ab (M44) known to exert agonist activity was capable of inducing IFN-gamma production by T cells when immobilized to plastic. Finally, CD30+CD4+ T cells exhibit significantly greater helper activity for B cell Ig production than CD30-CD4+ T cells. These results demonstrate that CD30 identifies a unique subset of T cells that comprise the major IFN-gamma- and IL-5-producing cells in the T cell compartment, and exhibit potent helper activity for B cell Ig production.