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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0801607v1 183/5/2915    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Gallagher, K. M. E. Articles by Godkin, A. J. PubMed PubMed Citation Articles by Gallagher, K. M. E. Articles by Godkin, A. J. Pubmed/NCBI databases Substance via MeSH

Type I Interferon (IFN) Acts Directly on Human Memory CD4⁺ T Cells Altering Their Response to Antigen¹

Department of Medical Biochemistry and Immunology, The Henry Wellcome Building, Cardiff University, Cardiff, United Kingdom

Despite its use widely as a therapeutic agent, and proposed use as vaccine adjuvant, the effect of IFN on T cell function is poorly understood. As a pleiotropic innate cytokine produced rapidly in response to pathogens, it is well placed to impinge on specific immune responses. The aim of this study was to examine the impact of IFN on the function of human memory CD4⁺ T cells using the recall Ags purified protein derivative, tetanus toxoid, and hemagglutinin. IFN administered either in vivo or added exogenously in vitro tended to enhance proliferative responses of purified protein derivative-specific T cells in marked contrast to the other cognate populations whose responses were often diminished. Purifying the memory CD4⁺CD45RO⁺ T cells confirmed IFN acted directly on these cells and not via an intermediate. The T cells could be divided into two broad categories depending on how IFN effected their responses to cognate Ag: 1) enhanced proliferation and a striking increase in IFN-production compared with smaller increases in IL-10 (increased ratio of IFN:IL-10), and 2) neutral or diminished proliferation coupled with a smaller increase in IFN relative to the increase in IL-10 (reduced IFN:IL-10 ratio). IFN has a role in modifying memory T cell responses when they are exposed to cognate Ag and may be important in vaccination strategies designed to augment particular Th memory responses.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

A.J.G. designed the research. K.G., S.L., and I.W.R. performed the research. K.M.E.G., A.M.G., and A.J.G. analyzed the data. K.M.E.G., A.M.G., and A.J.G. wrote the paper.

¹ This work was supported by research grants from Roche Pharmaceuticals, and Cardiff and Vale National Health Service Trust Research and Development department. A G. is a Medical Research Council Senior Fellow. Authors declare they have no financial conflict of interest.

² K.G. and S.L. contributed equally to this study.

³ Address correspondence and reprint requests to Dr. Andrew. J. Godkin, Department of Medical Biochemistry and Immunology, The Henry Wellcome Building, Cardiff University, Heath Park, Cardiff, United Kingdom. E-mail address: wmdajg{at}groupwise.cf.ac.uk

⁴ Abbreviations used in this paper: HCV, hepatitis C virus; PPD, purified protein derivative; TT, tetanus toxoid; HA, hemagglutinin.

⁵ The online version of this article contains supplementary material.