CD47 modulates OVA-specific lymphocyte proliferation and Th1/Th2 expression in children allergic to hen eggs

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Objective : CD47, known as integrin associated protein, is critically involved in T cell functions. The effect of CD47 antibody-ligation on ovalbumin (OVA)-stimulated T cell activation was investigated in egg-allergy (EA) children. Methods : OVA-stimulated antigen-presenting cells were recombinated. After a 6-day culture, cell division, Th1/Th2 expression and apoptosis were evaluated in carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay. Results : In EA children sensitive to OVA, ligation of CD47 in T cells by the monoclonal antibody (mAb) costimulate lymphocyte proliferation and reduced interferon (IFN)-gamma production when cells were activated in vivo by an extremely low cencentration of OVA (in vitro unstimulation), and in vitro by suboptimal cencentrations of OVA. When the cells were activated by a maximum mitogenic stimuli such as phytohemagglutinin (PHA), ligation of CD47 regulated cell proliferation. In contrast, in remitted patients after treatment with elimination diets, anergy in cell proliferation occurred antigen-specifically by ligation of CD47 molecules. Although cell survival, on stimulation with a higher concentration of OVA, was prolonged by CD47 Ab treatment in OVA-sensitive proliferative cells (CFSE-low cells) of active EA children, the OVA-activated cells (CFSE-high cells) were eliminated by enhanced apoptotic cell induction. CD47 molecules induced prolonged cell survival in unstimulated unproliferative cells in the OVA-tolerated status. Ligation of CD47 molecules also augmented chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH2)^+ cells on higher concentrations of OVA-activated cells (CFSE-high cells) in EA individuals. Thus, OVA-increased CRTH2^+ cells by treatment with CD47 Ab, is likely to transfer an activating signals to CRTH2^- cells reactive to OVA antigen and induce alive (apoptosis resistant) effector cell proliferation for egg allergy. In EA children after treatment with elimination diets, ligation of CD47 molecules induced chemokine receptor (CCR)5^+ cells on a low concentration of OVA-stimulated proriferative cells. Conclusions : In patients allergic to hen eggs, CD47 molecules have inhibitory effects in maximum stimuli, and have costimulatory effects to augment Th2 expression by suboptimal OVA-stimuli in antigen-specific lymphocyte proliferation and in contrast, in higher concentrations of OVA-stimuli, also enhance Th2 expression by augmented apoptosis of activated cells. In remitted patients CD47 signals induce anergy in cell proliferation antigen-specifically and Th1 expression by suboptimal stimuli.
北里大学の論文
2004-09-30

CD47 modulates OVA-specific lymphocyte proliferation and Th1/Th2 expression in children allergic to hen eggs

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