STRUCTURE AND EXPRESSION OF MURINE CD30 AND ITS ROLE IN CYTOKINE PRODUCTION

Murine CD30 cDNA predicts a protein of 498 amino acids with homology t o the TNF receptor family of proteins characterized by repeated cystei ne-rich motifs in the extracellular domain, Murine CD30, although homo logous to human CD30, has a 90 amino acid gap in an extracellular regi on that appears to be duplicated in human CD30, Murine CD30 cDNA was s hown to be functional through the production of a soluble murine Ig fu sion protein (CD30-Ig) that was active in binding to cells that expres sed CD30 ligand, CD30-Ig also served as an immunogen for the productio n of hamster anti-mouse CD30 mAbs, which recognized both CD30 expresse d by murine lymphocytes and CD30 expressed by cells transfected with m urine CD30 cDNA, CD30 mRNA is highly expressed in the thymus and in ac tivated spleen cells, but not in other tissues tested, In anti-CD3-act ivated spleen cells, CD30 ligand is expressed primarily by CD4(+) T ce lls, with peak expression at days 1 and 2, whereas CD30 is expressed p rimarily by CD8(+) T cells, with peak expression on days 4 and 5, Stim ulation of CD30 by plate-bound anti-CD30 directly signaled for IL-5 bu t not IFN-gamma production by CD30(+) CTL lines, These studies demonst rate that CD30 directs cytokine secretion and suggest that CD30 signal ing may be pivotal in the pattern of cytokine production by T cells.