| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Medicine, Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10021
Regulation of CD8 T cell expansion and contraction is essential for successful immune defense against intracellular pathogens. IL-10 is a regulatory cytokine that can restrict T cell responses by inhibiting APC functions. IL-10, however, can also have direct effects on T cells. Although blockade or genetic deletion of IL-10 enhances T cell-mediated resistance to infections, the extent to which IL-10 limits in vivo APC function or T cell activation/proliferation remains unknown. Herein, we demonstrate that primary and memory CD8 T cell responses following Listeria monocytogenes infection are enhanced by the absence of IL-10. Surface expression of the IL-10R is transiently up-regulated on CD8 T cells following activation, suggesting that activated T cells can respond to IL-10 directly. Consistent with this notion, CD8 T cells lacking IL-10R2 underwent greater expansion than wild-type T cells upon L. monocytogenes infection. The absence of IL-10R2 on APCs, in contrast, did not enhance T cell responses following infection. Our studies demonstrate that IL-10 produced during bacterial infection directly limits expansion of pathogen-specific CD8 T cells and reveal an extrinsic regulatory mechanism that modulates the magnitude of memory T cell 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.
1 This work was supported by National Institutes of Health Grants AI 39031 and AI 42135 (to E.G.P.).
2 Address correspondence and reprint requests to Dr. Eric Pamer, Department of Medicine, Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. E-mail address: pamere{at}mskcc.org
3 Abbreviations used in this paper: Tg, transgenic; DC, dendritic cell; LCMV, lymphocytic choriomeningitis virus.
This article has been cited by other articles:
|
|
 |
|
  A. Rivera, N. Collins, M. T. Stephan, L. Lipuma, I. Leiner, and E. G. Pamer Aberrant Tissue Localization of Fungus-Specific CD4+ T Cells in IL-10-Deficient Mice J. Immunol., July 1, 2009; 183(1): 631 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wahl, W. Muller, F. Leithauser, G. Adler, F. Oswald, J. Reimann, R. Schirmbeck, A. Seier, J. M. Weiss, B. Prochnow, et al. IL-20 Receptor 2 Signaling Down-Regulates Antigen-Specific T Cell Responses J. Immunol., January 15, 2009; 182(2): 802 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Popov, J. Driesen, Z. Abdullah, C. Wickenhauser, M. Beyer, S. Debey-Pascher, T. Saric, S. Kummer, O. Takikawa, E. Domann, et al. Infection of Myeloid Dendritic Cells with Listeria monocytogenes Leads to the Suppression of T Cell Function by Multiple Inhibitory Mechanisms J. Immunol., October 1, 2008; 181(7): 4976 - 4988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Joshi and S. M. Kaech Effector CD8 T Cell Development: A Balancing Act between Memory Cell Potential and Terminal Differentiation J. Immunol., February 1, 2008; 180(3): 1309 - 1315. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
