HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) All Versions of this Article: jimmunol.0902156v1 183/10/6554    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Nie, S. Articles by Selin, L. K. PubMed PubMed Citation Articles by Nie, S. Articles by Selin, L. K.

Resistance to Vaccinia Virus Is Less Dependent on TNF under Conditions of Heterologous Immunity¹

Siwei Nie,^* Markus Cornberg,^* and Liisa K. Selin^2*

*Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655; Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany

TNF has been shown to be important for controlling many pathogens. Here, we directly demonstrate using wild-type TNF^–/– and TNFR1^–/– mice that TNF does play a role in protection against vaccinia virus (VV) infection in naive mice. Since VV replication is also partially controlled in lymphocytic choriomeningitis virus (LCMV)-immune C57BL/6J mice through the process of heterologous immunity, we questioned whether TNF was required in mediating this protection. VV-infected LCMV-immune mice that were TNF-deficient as a consequence of genetic deletion or receptor blockade demonstrated normal recruitment and selective expansion of cross-reactive LCMV-specific memory CD8 T cells and controlled VV infection similar to LCMV-immune mice having TNF function. This indicates that neither TNF nor lymphotoxin, which uses the same receptor, was required in mediating protective heterologous immunity against VV. Indeed, prior immunity to LCMV made the role of TNF in protection against VV infection much less important, even under conditions of lethal dose inoculum. Thus, heterologous immunity may help explain why treatment of patients with anti-TNF compounds is reasonably well tolerated with relatively few infectious complications.

² Address correspondence to Dr. Liisa K Selin, Professor, Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655. E-mail address: Liisa.selin{at}umassmed.edu

¹ This study was supported by National Institutes of Health Grant AI-46578 (to L.K.S.), AI-46629 (to L.K.S.), and DFG fellowship CO310-1/1 (M.C.) (Germany). The contents of this publication are solely the responsibility of the authors and do not represent the official view of the National Institutes of Health.