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

嗜酸性粒细胞性胃肠疾病（EGID）是一组以胃肠道嗜酸性粒细胞炎症为特征的疾病。在过去的十年中，EGID的发病率急剧增加，特别是嗜酸性粒细胞性食管炎（EoE），但也有嗜酸性粒细胞性胃肠炎（EG）。EGID患者通常具有许多食物过敏，并且疾病随着基于氨基酸的元素饮食的建立而缓解。总之，这表明EGID是食物过敏原驱动的嗜酸性炎症性肠道疾病。 在我们以前的工作中，我们已经证明IL-5+ Th 2细胞与EGID相关，但与过敏性食物过敏无关。我们进一步将这些IL-5+ Th 2细胞表征为更高度分化的Th 2细胞，其是多轮抗原刺激的产物。总之，这些发现表明IL-5+ Th 2细胞可能是EGID中驱动嗜酸性肠道炎症的主要途径。然而，这些先前的研究仅限于血液T细胞。目前的工作正在进行中，以扩大这些发现肠道居民T细胞在嗜酸性胃肠道疾病患者。将获得GI活组织检查，并使用流式细胞术和细胞化学来确定是否存在与IL-5+ Th 2细胞的类似关联。 在合作工作中，我们应用多色流式细胞术技术用于表征其他免疫性疾病的EGID中的Th 2亚群。作为与寄生虫病实验室的Amy Klion博士小组合作的一部分，我们在一个不寻常的淋巴细胞嗜酸性粒细胞增多综合征病例中描述了克隆Th 2亚群的细胞因子表型。 作为与宿主防御实验室的Ash Jain博士小组合作的一部分，我们研究了激动性抗CD 40单克隆抗体对X连锁高IgM综合征（XHM）和胆道隐孢子虫病受试者的免疫调节作用。抗CD 40治疗导致Th 1细胞增加，2例受试者中有1例隐孢子虫短暂清除。

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.