Title

Cutting edge: elimination of an endogenous adjuvant reduces the activation of CD8 T lymphocytes to transplanted cells and in an autoimmune diabetes model

PubMed ID

16547223

UMMS Affiliation

Department of Pathology

Date

3-21-2006

Document Type

Article

Subjects

*Adjuvants, Immunologic; *Adoptive Transfer; Animals; Antigen-Presenting Cells; Antigens; Autoimmunity; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Line; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Lymphocyte Activation; Mice; Urate Oxidase; Uric Acid

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The generation of adaptive immune responses is thought to require the presence of adjuvants. Although microbial adjuvants are well characterized, little is known about what provides the adjuvant effect in responses to transplanted cells or in autoimmune diseases. It had been postulated that, in these situations, injured cells instead released "endogenous adjuvants." We previously identified uric acid as an endogenous adjuvant for coinjected Ags. We now report that elimination of uric acid reduced the generation of CTL to an Ag in transplanted syngeneic cells and the proliferation of autoreactive T cells in a transgenic diabetes model. In contrast, uric acid depletion did not reduce the stimulation of T cells to mature APCs or when endogenous APCs were activated with anti-CD40 Ab. These findings support the concept that danger signals contribute to the T cell responses to cell-associated Ags by activating APCs and identify uric acid as one of these signals.

Rights and Permissions

Citation: J Immunol. 2006 Apr 1;176(7):3905-8.

Related Resources

Link to Article in PubMed