Interleukin-3-producing CD4+ T-cells support eosinophil survival in a patient with transient hypereosinophilia

Abstract

A boy with idiopathic hypereosinophilia showed spontaneous resolution after 20 months and presented with an excess production of interleukin-3 from a small population of clonal CD3+CD4+T-cell receptor ab+ T-cells.A 9-month-old boy was referred to our hospital for evaluation of hypereosinophilia. Physical examination revealed a small number of reddish papules on his trunk; no other organ involvement was noted. Cardiac complications were not found despite periodic echographic monitoring. Results of the haematological examination showed a total leukocyte count of 57.0·10 9 cells/l with 81% eosinophils (46.2·10 9 cells/l). Examination of smears of peripheral blood and bone marrow aspirate showed an abundance of mature eosinophils and no blast cells. The possibility of secondary eosinophilia caused by allergic, toxic, parasitic, neoplastic or autoimmune disorders was ruled out. Results of immunophenotypic examination of circulating lymphocytes revealed no increase in unusual cells. Among the levels of eosinophilopoietic cytokines measured, plasma interleukin (IL)-3 level was increased (63 pg/ml, normal <31 pg/ml), while levels of IL-5 and granulocyte/macrophage-colony stimulating factor (GM-CSF) were undetectable. Culture supernatants of peripheral blood lymphocytes of the patient contained high levels of IL-3, whereas the levels of IL-5 and GM-CSF were undetectable. IL-3 was mainly produced from CD4+T-cell receptor (TCR) ab+ T-cells (Table 1). We established a series of T-cell lines producing mainly IL-3 from peripheral blood of the patient. Results of inverse PCR [2] and subsequent sequencing analysis showed that these T-cell lines carried the same complementary determining region 3 (CDR3) sequence of TCRb, suggesting that IL-3-producing T-cells were clonal. Since there were no obvious signs of serious organ involvement, no treatment was started. The patientÕs total eosinophil count gradually decreased and had returned to normal (<1.5·10 5 cells/l) by 20 months after the onset of illness. Concomitantly, levels of IL-3 in plasma and culture supernatant returned to normal and the clonal T-cells producing IL-3 disappeared from peripheral blood. No recurrence was observed during a 40-month follow-up period.Eosinophilia of more than 1.5·10 5 cells/l is characteristic of idiopathic hypereosinophilic syndrome (HES) persisting for at least 6 months without an identifiable underlying cause and with multiple-organ dysfunction [3]. Our case differed from classical HES because of the spontaneous resolution of eosinophilia and the absence of apparent organ dysfunction. Spontaneous remission of HES has been reported in a patient with brain involvement [6].Another peculiar feature of this case was that the hypereosinophilia was possibly caused by eosinophilopoietic cytokine IL-3. Previous studies have suggested that IL-5 is the principal cytokine inducing eosinophilia in HES [5]; however, the levels of IL-5 are not always increased in affected individuals [4]. Our case raises the possibility that IL-3 is a candidate cytokine that ...

IL‐5‐overexpressing mice exhibit eosinophilia and altered wound healing through mechanisms involving prolonged inflammation

“…T cells have previously been demonstrated to accumulate in wounds during the formation of granulation tissue, 23 and this may be exacerbated by the enhanced recruitment of eosinophils. Links between T cells and hypereosinophilia, 24 an idiopathic disease often manifesting lesions of the skin and epithelia, 25 suggests that CD4 + cells may be important regulators of eosinophil activity in wound healing.…”