Differential localization of colitogenic Th1 and Th2 cells monospecific to a microflora-associated antigen in mice
M Yoshida, Y Shirai, T Watanabe, M Yamori, Y Iwakura… - Gastroenterology, 2002 - Elsevier
M Yoshida, Y Shirai, T Watanabe, M Yamori, Y Iwakura, T Chiba, T Kita, Y Wakatsuki
Gastroenterology, 2002•ElsevierBackground & Aims: 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)-γ production or differentiated in vitro to T …
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)-γ production or differentiated in vitro to T …
Background & Aims
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)-γ 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-γ–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-γ 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.
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