Regulatory T cells modulate staphylococcal enterotoxin B-induced effector T-cell activation and acceleration of colitis.
Oral administration of bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) activates mucosal T cells but does not cause mucosal inflammation. We examined the effect of oral SEB on the development of mucosal inflammation in mice in the absence of regulatory T (Treg) cells. SCID mice were fed SEB 3 and 7 days after reconstitution with CD4(+) CD45RB(high) or CD4(+) CD45RB(high) plus CD4(+) CD45RB(low) T cells. Mice were sacrificed at different time points to examine changes in tissue damage and in T-cell phenotypes. Feeding SEB failed to produce any clinical effect on SCID mice reconstituted with CD4(+) CD45RB(high) and CD4(+) CD45RB(low) T cells, but feeding SEB accelerated the development of colitis in SCID mice reconstituted with CD4(+) CD45RB(high) T cells alone. The latter was associated with an increase in the number of CD4(+) Vbeta8(+) T cells expressing CD69 and a significantly lower number of CD4(+) CD25(+) Foxp3(+) T cells. These changes were not observed in SCID mice reconstituted with both CD45RB(high) and CD45RB(low) T cells. In addition, SEB impaired the development of Treg cells in the SCID mice reconstituted with CD4(+) CD45RB(high) T cells alone but had no direct effect on Treg cells. In the absence of Treg cells, feeding SEB induced activation of mucosal T cells and accelerated the development of colitis. This suggests that Treg cells prevent SEB-induced mucosal inflammation through modulation of SEB-induced T-cell activation.
Heriazon
Armando
A
Department of Medicine, Division of Gastroenterology, Mount Sinai Hospital, and Medical Sciences Division, University of Toronto, Canada.
Zhou
Pengfei
P
Borojevic
Rajka
R
Foerster
Katharina
K
Streutker
Catherine J
CJ
Ng
Terry
T
Croitoru
Kenneth
K
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003092:Colitis / Q000276:immunology* / Q000382:microbiology*; D004768:Enterotoxins / Q000494:pharmacology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
D015704:CD4 Antigens; D004768:Enterotoxins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; C031818:enterotoxin B, staphylococcal; D017493:Leukocyte Common Antigens