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.
St Mark's Hospital, Harrow, United Kingdom.
A L
AL
Hart
M A
MA
Kamm
S C
SC
Knight
A J
AJ
Stagg
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4