Mechanisms of allergy and clinical immunologyCD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation
Section snippets
CD34+ cell cultures
CD34+ progenitor cells were positively selected from umbilical cord blood by double passage through columns (Miltenyi Biotech, Auburn, Calif) leading to cellular preparations containing more than 98% CD34+ cells and negative for CD3, CD10, CD14, CD19, CD20, CD40, CD56, CD83, CDw125 (IL-5 receptor), and FcɛR1. CD34+ cells were cultured at 1 × 104 cells/mL in 0.2 mL in 96-well flat-bottom plates overnight in the presence of exogenous cytokines and neutralizing antibodies (+/−), as indicated.
Human CD34+ progenitor cells express functional receptors for TSLP and IL-33
Given the important role ascribed to TSLP and IL-33 in allergic diseases, we first sought to determine whether CD34+ cells expressed functional receptors for these cytokines. As shown in Fig 1, A, highly purified freshly isolated CD34+ cells expressed receptors for TSLP (TSLP-R and IL-7 Rα)21 and IL-33 (ST2 and IL-1 receptor accessory protein [AcP])22 at mRNA and protein levels. Overnight stimulation of freshly isolated CD34+ cells with TSLP in combination with IL-33 induced cytokine expression
Discussion
In steady-state conditions, hemopoietic progenitors constantly egress from BM into blood and circulate through the peripheral tissues, where they may differentiate into tissue-resident cells. In allergic diseases, the BM releases increased numbers of CD34+ progenitors that migrate to the sites of allergic inflammation, where they differentiate into MCs, eosinophils, and basophils, the typical effector cells of allergic responses. The current data indicate that in addition to being hemopoietic
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Supported by a grant from Amgen Inc. Z.A. is a recipient of the Parker B. Francis fellowship.
Disclosure of potential conflict of interest: M. R. Comeau is employed by Amgen, Inc. L. M. Endam and M. Derosiers have received research support from the Foundation Antoine Turmel. G. M. Gauvreau has served as a consultant for MedImmune, Icagen, and Altair and has received research support as an investigator from Schering-Plough and MedImmune. The rest of the authors have declared that they have no conflict of interest.