Mechanisms of cytokine-mediated localized immunoprotection

نویسنده

  • N Sarvetnick
چکیده

T he actions ofproinflammatory or regulatory cytokines have been quite unpredictable when expressed individually within tissues such as in transgenic mice. Cytokines that have been considered proinflammatory in the classical sense have been shown to have immunosuppressive effects; likewise, cytokines that have demonstrated immunosuppressive activity have proven to be proinflammatory in these transgenic experimental systems (1). In this issue, studies on elicitation of the cytokine tumor necrosis factor-0~ (TNF-o 0 within the context of pancreatic islets elegantly illustrate this paradox (2). The proinflammatory cytokine TNF-cx, long associated with phenomena such as autoimmunity, cell death, and cachexia shows quite unexpected characteristics in this transgenic system. In the current study, it was demonstrated that within the limited context of the pancreatic islets, TNF-o~ prevents the development of diabetes in the most widely studied animal model of the spontaneous disease: the nonobese diabetic (NOD) mouse. This work is important for several additional reasons other than the unpredicted ability of this cytokine to divert the nearly inevitable autoimmune responses that mediate disease in the N O D mouse. The data presented in this paper support a unique mechanism of disease amelioration, although a full picture will have to await additional studies. Previous work by these authors with the identical transgene harbored by nondiabetes-prone mice has highlighted the proinflammatory nature of TNF-ci because the cytokine was demonstrated to induce inflammation and leukocyte extravasation in these animals (3). This was probably mediated through the induction of adhesion molecules that support leukocyte extravasation into the pancreas. Insulitis resulted and progressed to be quite severe. Although these lymphocytes traffic in large numbers into the islet region, they are unable to promote killing of sufficient numbers of beta cells to induce any hyperglycemia despite their ability to cross into the actual islet parenchyma core and disrupt the islet architecture. Thus, on a nonsusceptible genetic background, severe infiltration does not promote disease.

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عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 184  شماره 

صفحات  -

تاریخ انتشار 1996