Variation in Gut‐Homing CD27‐Negative Lymphocytes in Inflammatory Colon Disease

Abstract

Prolonged antigenic stimulation results in lymphocyte shedding of CD27, a member of the tumour necrosis factor receptor (TNFR) family, and transformation to a stable phenotype capable of synthesizing interleukin-4 (IL-4). Co-expression of alpha4beta7 identifies those cells with gut-homing potential. We have investigated these cell populations in patients with inflammatory colonic disease. Circulating and lamina propria mononuclear cells were isolated from patients with Crohn's disease (CD), ulcerative colitis (UC), non-inflammatory bowel disease (non-IBD) colonic inflammation and healthy controls. Double and triple colour flow cytometry for CD3, CD4, CD27, alpha4beta7 and intracellular cytokines was performed. Circulating CD4+ CD27- populations were increased in patients with CD (8.8 +/- 0.8%, P < 0.001), UC (12.2 +/- 1.9%, P < 0.001) and non-IBD colitis (10.5 +/- 1.3%, P < 0.01) as compared with controls (6.1 +/- 0.5%). CD4+ CD27- alpha4beta7+ cells were increased in CD (P < 0.01). Lamina propria CD4+ CD27- populations were depressed significantly in CD (P < 0.05), UC (P < 0.02) and non-IBD colitis (P < 0.03). Mucosal CD4+ CD27- cells synthesized IL-4 in preference to interferon-gamma. Thus, colonic inflammation is associated with alterations in gut-tropic circulating and mucosal populations of differentiated memory T cells with the phenotype of predominantly IL-4-synthesizing cells.

Heterogeneity of Circulating CD4+ Memory T-Cell Subsets in Erythrodermic Patients: CD27 Analysis Can Help to Distinguish Cutaneous T-Cell Lymphomas from Inflammatory Erythroderma

“…This observation is in agreement with previous data [27 ]showing that after prolonged in vitro activation CD27 is gradually down-regulated. Likewise, an increase in the CD4+CD27– subset has been described in pathological conditions of persistent antigenic stimulation, such as in systemic lupus erythematosus [6], Crohn’s disease or ulcerative colitis [28]. To further investigate the significance of a prolonged antigenic stimulation, any possible influence of age on the results had to be excluded, as it is known that both CD4+CD27– and TEM subsets increase in healthy subjects [4 ]as they age.As expected [4], healthy subjects showed a significant increase in CD27– and TEM populations with the increase in age.…”

Flow cytometric measurement of intracellular migration inhibition factor and tumour necrosis factor alpha in the mucosa of patients with coeliac disease

“…The techniques employed previously for analysis of proinflammatory cytokines in coeliac disease were in situ hybridization [4,5], immunohistochemistry [3] and ELISPOT [20]. Detection of intracellular cytokines, using flow cytometry, has recently been used in quantification of proinflammatory cytokines in diseases such as malaria [21], inflammatory bowel disease [22] and atopic dermatitis [23]. This technique involves the use of permeabilized cells which together with monoclonal antibodies to cell surface markers can be used to identify the cellular origin of cytokine production.…”

Naive T Cells in the Gut of Newly Diagnosed, Untreated Adult Patients with Inflammatory Bowel Disease

“…In CD, the major cytokines interferon g (IFN-g) and interleukin 17 (IL-17) are derived from T helper 1 (Th1) and Th17 cell differentiation, respectively, 14 whereas UC has been shown to be predominantly driven by a Th2-like differentiation process, leading to the expansion of natural killer T cells and production of the cytokines IL-4 and IL-13. [17][18][19] Here, we have determined the distribution of different T-cell subpopulations and their related cytokine profiles in the gastrointestinal mucosa of newly diagnosed, untreated adult patients with IBD. 8,14 Notably, these immunologic typologies were mainly based on experimental studies in murine models, 15,16 whereas, studies on T cells in the intestinal mucosa of humans have typically been performed in patients with IBD who were under treatment with immune-modulating therapies.…”