Differential localization of colitogenic Th1 and Th2 cells monospecific to a microflora-associated antigen in mice.
OBJECTIVE
Clonal expansion of T cells is associated with inflammatory bowel diseases, which indicates antigenic activation of the T cells. We investigated whether the introduction of CD4 T cells specific to a microflora would initiate colitis and assessed the cytokine requirements for colitogenic CD4 T cells.


METHODS
Severe combined immunodeficiency disease (SCID) mice were reconstituted with CD4 T cells, which were either deficient in interleukin (IL)-4/interferon (IFN)-gamma production or differentiated in vitro to T-helper (Th) 1/Th 2 and bearing a transgenic T-cell receptor (TCR) specific to ovalbumin (OVA), and then inoculated with an Escherichia coli-producing OVA (ECOVA). Clinical and histologic manifestations of colitis were assessed.


RESULTS
Mice with ECOVA colonization and OVA-specific CD4 T cells developed colitis with histologic features of focal infiltration by mononuclear cells, destruction of crypts, and loss of goblet cells. Further, infiltration was initiated in pre-existing lymph follicles. Th1- and IL-4 deficient T cells were diffusely localized in the lamina propria and submucosa, whereas Th2- and IFN-gamma-deficient T cells were localized preferentially in lymph follicles.


CONCLUSIONS
A microbe-associated antigen, non-cross-reactive to colonic tissue, can drive antigen-specific CD4 T cells to cause colitis in SCID mice. Although the presence of IFN-gamma and IL-4 in the effector CD4 T cells was not an absolute requirement for the development of colitis, they seemed to regulate it in part by modulating migration of the effector T cells.
Yoshida
Masaru
M
Division of Clinical Bio-regulatory Science, Graduate School of Medicine, Kyoto University, Japan.
Shirai
Yasuhiko
Y
Watanabe
Tomohiro
T
Yamori
Masashi
M
Iwakura
Yoichiro
Y
Chiba
Tsutomu
T
Kita
Toru
T
Wakatsuki
Yoshio
Y
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000172:deficiency; D051379:Mice; D016513:Mice, SCID; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*; D019282:Wasting Syndrome / Q000276:immunology
D000942:Antigens, Bacterial; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin