IL-5 expressed by CD4⁺ lymphocytes from Echinococcus multilocularis-infected patients

Abstract

IL-5 is a major factor inducing differentiation of B lymphocytes into immunoglobulin-producing cells as well as a main regulator of eosinophils. Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with alveolar echinococcosis (AE) express IL-5 mRNA after stimulation with crude Echinococcus multilocularis (E.m.) antigen. To characterize the observed response in lymphocyte subpopulations, we cultured patients' PBMC in the presence of E.m. crude antigen for 18 h. PBMC were separated from seven patients by fluorescence-activated cell sorting (EPICSorter) into CD4⁺ and CD8⁺ subpopulations and from an additional seven patients by magnetic cell sorting (MACS) into CD4⁺, CD8⁺ and the CD4⁺/CD8⁺ depleted fractions. mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) for the cytokines IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, as well as for β-actin as control. IL-4 and IFN-γ expression was positive in all of the patients in the stimulated CD4⁺ subgroup. IL-5 mRNA expression was detected in eight out of 14 CD4⁺ samples (58%) and not observed in the other subpopulations, or the unstimulated and healthy controls. Co-expression of other Th2 cytokines in the eight patients expressing IL-5 mRNA was found in five patients for IL-3 and in seven for IL-10. Expression of IL-5 and both Th2 cytokines (IL-3 and IL-10) was only observed in patients judged as critically ill. Out of the six patients who were regarded as cured after radical operation or as stabilized with or without chemotherapy, only two expressed IL-5. Out of those eight patients considered as critically ill, six expressed IL-5 mRNA and five of these co-expressed IL-3 and IL-10. Thus, we conclude that specific antigenic challenge of PBMC from patients with active or previous AE induces an IL-5 response of CD4⁺ lymphocytes. The expression of Th2-type interleukin mRNA is significantly more frequent in patients clinically judged as progressive. Furthermore, IgE was elevated only in patients regarded as critically ill (six out of eight). In none of the patients were eosinophils elevated. These data support a Th2-type immune response in patients with chronic E. multilocularis infection.

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