Variation in gut-homing CD27-negative lymphocytes in inflammatory colon disease.
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.
Meenan
J
J
Department of Gastroenterology, St Thomas' Hospital, London, UK.
Spaans
J
J
Grool
T A
TA
Lammers
K
K
Pals
S
S
Tytgat
G N
GN
van Deventer
S J
SJ
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000648:ultrastructure; D003093:Colitis, Ulcerative / Q000276:immunology; D003106:Colon / Q000166:cytology; D003424:Crohn Disease / Q000276:immunology; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D016023:Integrins / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007413:Intestinal Mucosa / Q000276:immunology; D007424:Intracellular Fluid / Q000737:chemistry; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology*; D008297:Male; D018523:Tropism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
D016023:Integrins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C071777:integrin alpha4beta7; D015847:Interleukin-4; D007371:Interferon-gamma