부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jaut.2008.06.002 Byline: Patricia A. Gonnella, Hanspeter Waldner, Pedro J. del Nido, Francis X. McGowan Abstract: Toll-like receptors (TLR) are pattern recognition receptors that are an essential feature of host defense against pathogens. Expression of TLR-4 on dendritic cells was reported to be required for initiation of experimental autoimmune myocarditis (EAM) but the mechanism by which TLR-4 signaling affects autoimmunity is incompletely understood. To determine the role of TLR-4 in EAM, wild type and TLR-4.sup.-/- mice were immunized with myosin peptide (614-629) in CFA. TLR-4.sup.-/- mice demonstrated decreased myosin specific proliferation and decreased production of INF-[gamma] and IL-2. Immunization with myosin induced greater severity of myocarditis in wild type compared to TLR-4.sup.-/- mice as evidenced by lesions in the myocardium. TcR V[beta] 8.1, 8.2.sup.+ CD4.sup.+ T cells, detected in lesions were isolated from splenocytes by flow cytometry and found to undergo increased apoptosis in TLR-4.sup.-/- mice. In situ immunohistochemistry showed increased colocalization of cleaved caspase 3 and TcR V[beta] 8.1, 8.2.sup.+ CD4.sup.+ T cells in TLR-4.sup.-/- mice compared to wild type. Increased apoptosis was associated with impaired activation of NF-kB p65 and decreased cell viability in the presence of TNF-[alpha]. These results demonstrate that infiltrating TcR V[beta] 8.1, 8.2.sup.+ CD4.sup.+ T cells are deleted by the mechanism of apoptosis in TLR-4.sup.-/- mice with EAM. Author Affiliation: Department of Anesthesiology, Children's Hospital and Harvard Medical School, 320 Longwood Ave., Boston, MA 02115, USA Article History: Received 1 April 2008; Revised 13 June 2008; Accepted 30 June 2008