Quantitative and functional characteristics of intestinal-homing memory T cells: analysis of Crohn's disease patients and healthy controls.
Circulating memory T cells can be subdivided on the basis of beta7 integrin expression. The beta7+ population contains cells primed in the intestine capable of homing back to the gut. We hypothesized that cytokine production by beta7+ memory T cells reflects the specialized mucosal compartment in which they were primed. Flow cytometry of whole blood was used to assess numbers of beta7+ (beta7hi and beta7int) and beta7- memory T cells and their production of Th1 and regulatory cytokines in healthy controls and Crohn's disease patients. In controls, beta7+ and beta7- memory T cells displayed a similar qualitative profile of cytokine production but the beta7+ population was enriched for cytokine-producing effector cells. In addition, the beta7hi population contained more cytokine-producing cells than the beta7int population, suggesting a gradient of cytokine production based on beta7 integrin expression. In active Crohn's disease, there was altered expression of beta7 integrin with a decrease in intestinal-homing memory T cells and an increase in systemic memory T cells. Furthermore, there was a selective loss of IL-10 and increase in TGF-beta in both beta7+ and beta7- memory T cell subsets which may contribute to the pathogenesis of the inflammatory process in Crohn's disease.
Hart
A L
AL
St Mark's Hospital, Watford Road, Harrow, UK.
Kamm
M A
MA
Knight
S C
SC
Stagg
A J
AJ
D000328:Adult; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007156:Immunologic Memory / Q000276:immunology*; D039641:Integrin beta Chains / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D016207:Cytokines; D039641:Integrin beta Chains; D016212:Transforming Growth Factor beta; C091368:integrin beta7; D016753:Interleukin-10