Expression of CD45RB functionally distinguishes intestinal T lymphocytes in inflammatory bowel disease.
The importance of CD45RB expression on T cells was already shown in mice where CD45RB(high) expression determines pathogenic potential. In this study, we analyzed the expression of CD45RA, CD45RB, and CD45RO on CD4(+) T lymphocytes in the intestinal mucosa and in the circulation of patients with inflammatory bowel disease (IBD). In addition, we studied the cytokine profile of these cells. In the circulation, virtually all CD4(+)CD45RB(high) T cells expressed the naive marker CD45RA, and circulating CD4(+)CD45RB(low) cells expressed the memory marker CD45RO in IBD patients and a control patient population. In contrast, the intestinal CD4(+) CD45RB(high) T cells are in normal controls for 90% CD45RO(+). However, in IBD, 27.7% [Crohn's disease (CD)] and 49% [ulcerative colitis (UC)] of the intestinal CD4(+) CD45RB(high) T cells are CD45RA(+). This special CD4CD45RA(+) T cell in IBD can be found in the lamina propria as well as in lymphoid follicles (confocal laser-scanning microscopy). The CD4(+)CD45RB(high) T lymphocytes produce significantly less interleukin (IL)-10 and IL-4 and produce more tumor necrosis factor alpha than CD45RB(low) T lymphocytes in control patients. CD4(+)CD45RB(low) T cells from IBD patients produced less IL-10 than CD4(+)CD45RB(low) T lymphocytes of controls, and interferon-gamma production by both T lymphocyte subsets was decreased in IBD. These data indicate that CD and UC are characterized by an influx of CD4(+)CD45RB(high) T lymphocytes. These CD4(+)CD45RB(high) T lymphocytes seem to be important in the pathogenesis of IBD, as they produce more proinflammatory cytokines and less anti-inflammatory cytokines compared with CD4(+)CD45RB(low) T lymphocytes.
Ten Hove
Tessa
T
H2-256, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
The Olle
F
F
Berkhout
Marloes
M
Bruggeman
Joost P
JP
Vyth-Dreese
Florry A
FA
Slors
J Frederik M
JF
Van Deventer
Sander J H
SJ
Te Velde
Anje A
AA
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000276:immunology*; D003424:Crohn Disease / Q000097:blood / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D017493:Leukocyte Common Antigens