GSBS Student Publications

Title

Type 1 IFN mediates cross-talk between innate and adaptive immunity that abrogates transplantation tolerance

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Medicine, Division of Diabetes; Department of Pathology; Department of Molecular Genetics and Microbiology; Department of Medicine, Division of Endocrinology and Metabolism

Date

11-6-2007

Document Type

Article

Medical Subject Headings

Animals; CD8-Positive T-Lymphocytes; Graft Survival; *Immunity, Natural; Interferon Inducers; Interferon Type I; Lipopolysaccharides; Mice; Mice, Knockout; Myeloid Differentiation Factor 88; Poly I-C; Receptor, Interferon alpha-beta; Signal Transduction; Skin Transplantation; Toll-Like Receptor 3; Toll-Like Receptor 4; *Transplantation Tolerance; Transplantation, Homologous

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

TLR activation of innate immunity prevents the induction of transplantation tolerance and shortens skin allograft survival in mice treated with costimulation blockade. The mechanism by which TLR signaling mediates this effect has not been clear. We now report that administration of the TLR agonists LPS (TLR4) or polyinosinic:polycytidylic acid (TLR3) to mice treated with costimulation blockade prevents alloreactive CD8(+) T cell deletion, primes alloreactive CTLs, and shortens allograft survival. The TLR4- and MyD88-dependent pathways are required for LPS to shorten allograft survival, whereas polyinosinic:polycytidylic acid mediates its effects through a TLR3-independent pathway. These effects are all mediated by signaling through the type 1 IFN (IFN-alphabeta) receptor. Administration of IFN-beta recapitulates the detrimental effects of TLR agonists on transplantation tolerance. We conclude that the type 1 IFN generated as part of an innate immune response to TLR activation can in turn activate adaptive immune responses that abrogate transplantation tolerance. Blocking of type 1 IFN-dependent pathways in patients may improve allograft survival in the presence of exogenous TLR ligands.

Rights and Permissions

Citation: J Immunol. 2007 Nov 15;179(10):6620-9.

Related Resources

Link to Article in PubMed

Journal Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

17982052