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

Abstract

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.

Induction of Functional IL-8 Receptors by IL-4 and IL-13 in Human Monocytes

“…6, A and B). On the contrary, in Omenn's syndrome the macrophages and dendritic cells that typically accumulate within lymph nodes (43) showed strong reactivity for CXCR1 mAb (Fig. 6C).…”

“…This hypothesis is supported by the demonstration that monocyte-derived cells and dendritic cells express IL-8 receptors in Omenn's syndrome and atopic dermatitis, two pathological conditions typically characterized by a Th2-dominated immune response and IL-4 production (43,44,61).…”

“…Finally, to gain insight into the possible in vivo relevance of these results, the expression of IL-8 receptors was investigated in two Th2-skewed pathologies characterized by the presence of IL-4 and IL-13, namely the Omenn's syndrome and atopic dermatitis (43,44). As expected, on the basis of the observations obtained in vitro, in normal tissues IL-8 receptor expression was detected only on neutrophils, whereas various monocyte-derived cells (e.g., tingle-body macrophages of germinal centers; interstitial macrophages) and dendritic cells (e.g., interdigitating dendritic cells and Langerhans cells) resulted completely negative (Fig.…”

CD30 triggering by agonistic antibodies regulates CXCR4 expression and CXCL12 chemotactic activity in the cell line L540

“…9,13 The IL-4 requirement is probably the reason for the association of CD30 expression with preferential Th0-and Th2-type immune responses in vitro 8 and in vivo. [14][15][16] Stimulation of CD30 by CD153 (CD30 ligand) leads to nuclear mobilization of NF-B complexes 17 while inducing a signal-coupled depletion of TRAF2, which increases the cell sensitivity to TNFR1-dependent apoptosis. 3 This dual signaling may explain the pleiotropic effects after CD30 stimulation in CD30 ϩ lymphoma cell lines 18 and T cells, the latter acquiring a Th2-type function, 19 associated with inhibitory functions, 20 based on impaired clonal expansion of T cells.…”

Successful unrelated cord blood transplantation in two children with severe combined immunodeficiency syndrome

“…10 Omenn-like syndrome is the engraftment of maternal T-cells in a child with a T-SCID, which is clinically reminiscent of Omenn syndrome. [11][12] Case report…”