CD30 cell expression and abnormal soluble CD30 serum accumulation in Omenn's syndrome: Evidence for a T helper 2-mediated condition

Omenn's syndrome (OS) is a severe immunodeficiency. characterized by clinical and laboratory features reminiscent of a T helper type-2 (Th2) response. CD30. a member of the tumor necrosis factor receptor superfamily. has been found to be preferentially expressed by human T cell clones exhibiting a Th2-like profile and function. We investigated whether there are derangement in CD30 expression in tissues. and/or abnormalities in soluble CD30 (sCD30) levels in the serum. or both, of three children with OS and one child with maternal engraftment and Omenn's-like syndrome (OLS). Large proportions of tissue-infiltrating T lymphocytes from all four patients expressed CD30. whereas in control tissues. including peripheral blood. CD30 T lymphocytes were extremely few or absent. In addition. levels of sCD30 were abnormally increased in all patients sera. T cell clones were generated from sorted CD30(-) and CD30(-) peripheral blood T cells of the patient with OLS who showed unusually high numbers of circulating CD30(-) T lymphocytes. Most CD4(-) T cell clones derived from CD30(-) cells showed a Th2-like cytokine profile. whereas the majority of clones generated from CD30(-) T cells were Th1. These findings support the hypothesis that Th2 cells are involved in the pathogenesis of OS. Moreover. they provide evidence that detection of CD30(-) T cells in tissues. increased levels of sCD30 in biological fluids. or both, reflect the presence of immune responses characterized by prevalent activation of T cells producing Th2 cytokines.