Dissecting the Heterogeneity in T-Cell Mediated Inflammation in IBD

Infiltration of the lamina propria by inflammatory CD4⁺ T-cell populations is a key characteristic of chronic intestinal inflammation. Memory-phenotype CD4⁺ T-cell frequencies are increased in inflamed intestinal tissue of IBD patients compared to tissue of healthy controls and are associated with disease flares and a more complicated disease course. Therefore, a tightly controlled balance between regulatory and inflammatory CD4⁺ T-cell populations is crucial to prevent uncontrolled CD4⁺ T-cell responses and subsequent intestinal tissue damage. While at steady state, T-cells display mainly a regulatory phenotype, increased in Th1, Th2, Th9, Th17, and Th17.1 responses, and reduced Treg and Tr1 responses have all been suggested to play a role in IBD pathophysiology. However, it is highly unlikely that all these responses are altered in each individual patient. With the rapidly expanding plethora of therapeutic options to inhibit inflammatory T-cell responses and stimulate regulatory T-cell responses, a crucial need is emerging for a robust set of immunological assays to predict and monitor therapeutic success at an individual level. Consequently, it is crucial to differentiate dominant inflammatory and regulatory CD4⁺ T helper responses in patients and relate these to disease course and therapy response. In this review, we provide an overview of how intestinal CD4⁺ T-cell responses arise, discuss the main phenotypes of CD4⁺ T helper responses, and review how they are implicated in IBD.