00318732

open access

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Tolerance Mechanisms in Murine Autoimmune Diabetes Induced by Anti-ICAM-1/LFA-1 mAb and Anti-CD8 mAb

English (英語)

The Kobe journal of the medical sciences

48(5/6)

167-175

Kobe University School of Medicine

2003-01

2006-07-15

A short-term administration of antibodies against ICAM-1/LFA-1 or CD8 molecules during a critical period of younger age resulted in complete protection of autoimmune diabetes in NOD mice. In this study, we attempted to elucidate the tolerance mechanisms. Transfer of splenocytes from both antibody-treated NOD mice to NOD-SCID mice failed to develop diabetes. On the other hand, when splenocytes from diabetic mice were transferred to the antibody-treated mice, 40% of both mAb-treated recipients became diabetic. In vitro response of T cells from these protected mice exhibited strong proliferation against syngeneic islet cells or ConA. Furthermore, semiquantitative RT-PCR analysis of cytokines showed that T cells from anti-CD8-treated mice could express IFN-γ, IL-4, IL-10 and TGF-β1 in response to islet antigen. In contrast, T cells from anti-ICAM-1/LFA-1-treated mice expressed IFN-γ, IL-10 and TGF-β1 but not IL-4. These results suggest that tolerance mechanisms like clonal deletion, anergy, immunoregulatory T cells or Th1 to Th2/Th3 cytokine shifting are not responsible for the tolerance induction, indicating the presence of other unrevealed mechanism responsible for the loss of capability of autoreactive T cells to infiltrate and destroy the pancreatic β-cells in vivo.

tolerance

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