Ex vivo simulation of IgG Fc and T-cell receptor functions: An application to inflammatory bowel disease

Abstract

Background: Human leukocyte IgG Fc receptors (FcγR) and T-cell receptors (TCR) are primary molecules involved in inflammatory and immune pathways. Methods: These 2 receptors were stimulated in whole blood for 2-4 hours with immune complex and specific agonistic antibody, respectively, and various mRNAs were quantified by a method we developed previously. Results: FcγR stimulation induced tumor necrosis factor superfamily 2 (TNFSF2), TNFSF8, TNFSF15, interleukin 1B (IL1B), IL8, CCL chemokine 2 (CCL2), CCL3, CCL4, CCL11, CCL20, CXCL chemokine 1 (CXCL1), CXCL2, and CXCL3 mRNA, whereas TCR stimulation induced different subsets of mRNA such as TNFSF1, TNFSF2, TNFSF5, TNFSF6, TNFSF9, TNFSF14, IL6, CCL2, CCL8, CCL20, and CXCL10. Interestingly, respondents and nonrespondents were identified for each mRNA. When we applied this method to inflammatory bowel disease, the respondent populations of TCR-induced TNFSF2 (= TNFα), TNFSF5, TNFSF14, CCL2, CCL8, and CCL20 mRNA were significantly higher in Crohn's disease (CD) patients than in healthy controls or those with ulcerative colitis (UC). No difference was found for FcγR-mediated responses. The respondent population of TCR-induced TNFSF2 showed significantly (P = 0.05) higher incidence of multiple surgeries than did nonrespondents. Conclusions: These data demonstrate an underlining hyperfunction of TCR in peripheral-blood leukocytes in CD patients. The ex vivo simulation demonstrates an underlining hyperfunction of TCR in peripheral-blood leukocytes in CD patients and may form the basis of a relatively noninvasive test for distinguishing these IBDs. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.