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-line 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.
Chilosi
M
M
Department of Pathology, University of Verona, Italy.
Facchetti
F
F
Notarangelo
L D
LD
Romagnani
S
S
Del Prete
G
G
Almerigogna
F
F
De Carli
M
M
Pizzolo
G
G
D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D017730:Ki-1 Antigen / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000276:immunology* / Q000473:pathology; D012995:Solubility; D013577:Syndrome; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D017730:Ki-1 Antigen