Prospective evaluation of intestinal homing memory T cells in ulcerative colitis

BACKGROUND: Intestinal homing (beta7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (beta7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. METHODS: Twelve patients with frequently relapsing ulcerative colitis (> or = 2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify beta7+ cells and beta7- populations within CD3+CD45RA- leukocytes. Production of cytokines (IFN-gamma, TNF-alpha, IL-2, IL-10, TGF-beta, and IL-4) was determined by intracellular labeling. RESULTS: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of beta7+:beta7- memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing beta7+ memory T cells produced IL-4 (p < 0.02) and TNF-alpha (p < 0.05) at disease relapse compared with remission. Non-intestinal homing beta7- memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. CONCLUSIONS: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-alpha and TH2 (IL-4) cytokines by intestinal homing beta7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis.