Highly differentiated IL5+ Th2 cells in food allergy and eosinophilic GI disease

嗜酸性胃肠道疾病(EGID)是一组以胃肠道嗜酸性炎症为特征的疾病。在过去的十年中，EGID的发病率急剧上升，尤其是嗜酸性食管炎(EoE)，但也有嗜酸性胃肠炎(EG)。EGID患者通常有许多食物过敏，随着以氨基酸为基础的元素饮食的建立，疾病进入缓解状态。综上所述，这表明EGID是一种由食物过敏原引起的嗜酸性炎症性肠病。 在我们之前的工作中，我们已经证明了IL-5+Th2细胞与EGID有关，但与食物过敏形式无关。我们进一步将这些IL-5+Th2细胞定性为更高分化的Th2细胞，是多轮抗原刺激的产物。综上所述，这些发现提示IL-5+Th2细胞可能是导致EGID患者嗜酸性肠炎的主要途径。然而，这些先前的研究仅限于血液T细胞。目前正在进行的工作是将这些发现扩展到嗜酸性胃肠道疾病患者的肠道驻留T细胞。将获得胃肠道活检，并将使用流式细胞术和免疫组织化学来确定是否存在与IL-5+Th2细胞类似的关联。 在合作工作中，我们已经将用于表征EGID中Th2亚群的多色流式细胞术技术应用于其他免疫性疾病。作为与艾米·克莱恩博士在寄生虫病实验室的合作的一部分，我们已经确定了一例罕见的淋巴细胞高嗜酸性粒细胞综合征患者的克隆性Th2亚群的细胞因子表型。作为与Ash Jain博士在宿主防御实验室的合作的一部分，我们在X连锁高IgM综合征(XHM)和胆道隐孢子虫病患者中检测了一种激动型抗CD40单抗对免疫调节的作用。抗CD40抗体治疗后Th1细胞数量增加，2名受试者中有1名隐孢子虫瞬时清除。

Eosinophilic gastrointestinal disorders (EGIDs) are a group of diseases characterized by eosinophilic inflammation of the gastrointestinal tract. In the past decade, there has been a dramatic increase in the incidence of EGIDs, particularly eosinophilic esophagitis (EoE), but also eosinophilic gastroenteritis (EG). EGID patients often have numerous food hypersensitivities, and the disease goes into remission with the institution of an amino acid based elemental diet. In sum, this suggests that EGID is a food allergen driven eosinophilic inflammatory gut disease. In our previous work we have demonstrated that IL-5+ Th2 cells are associated with EGID, but not anaphylactic forms of food allergy. We have further characterized these IL-5+ Th2 cells as more highly differentiated Th2 cells that are the product of multiple rounds of antigenic stimulus. In sum, these findings suggest that IL-5+ Th2 cells may be the major pathway driving eosinophilic gut inflammation in EGID. However, these previous investigations have been limited to blood T cells. Current work is underway to extend these findings to gut resident T cells in patients with eosinophilic GI disease. GI biopsies will be obtained and both flow cytometry and immunohistochemisty will be used to determine if a similar association with IL-5+ Th2 cells exists. In collaborative work we have applied the polychromatic flow cytometry techniques used to characterized Th2 subpopulations in EGID to other immunological diseases. As part of a collaboration with Dr. Amy Klion's group in the Laboratory of Parasitic Diseases, we have characterized the cytokine phenotype of the clonal Th2 subpopulation in an unusual case of lymphocytic hypereosinophilic syndrome. As part of a collaboration with Dr. Ash Jain's group in the Laboratory of Host Defenses, we have examined immunomodulation by an agonistic anti-CD40 monoclonal antibody in subjects with X-linked hyper-IgM syndrome (XHM) and biliary Cryptosporidiosis. Treatment with anti-CD40 resulted in an increased in Th1 cells and in 1 of 2 subjects, transient clearing of the Cryptosporidia.