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

This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lerner, C. G. Articles by Powell, J. D. Search for Related Content PubMed PubMed Citation Articles by Lerner, C. G. Articles by Powell, J. D. Pubmed/NCBI databases Substance via MeSH

Distinct Requirements for C-C Chemokine and IL-2 Production by Naive, Previously Activated, and Anergic T Cells

Cara G. Lerner^*, Maureen R. Horton, Ronald H. Schwartz^* and Jonathan D. Powell^1,*

^* Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Pulmonary Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Ag presented by activated APCs promote immunogenic responses whereas Ag presented by resting APCs leads to tolerance. In such a model, the regulation of cytokine release by the presence or absence of costimulation might potentially play a critical role in dictating the ultimate outcome of Ag recognition. C-C chemokines are a structurally defined family of chemoattractants that have diverse effects on inflammation. We were interested in determining the activation requirements for chemokine production by CD4⁺ T cells. Our data demonstrate for T cell clones and previously activated T cells from TCR-transgenic mice that stimulation with anti-TCR alone results in the production of copious amounts of macrophage-inflammatory protein-1 (MIP-1) and other C-C chemokines, and that addition of anti-CD28 gives very little augmentation. Furthermore, MIP-1 production is nearly equivalent from both anergic and nonanergic cells. For naive T cells, anti-CD3 stimulation alone led to as much MIP-1 production as Ag + APC stimulation. The addition of costimulation gave a 3–10-fold enhancement, but this was 70-fold less than the effect of costimulation on IL-2 production. Thus, although C-C chemokines play a broad role in influencing inflammation, their production by signal 1 alone makes them unlikely to play a critical role in the decision between a tolerogenic and an immunogenic response. Furthermore, the production of MIP-1 by anergic T cells, as well as following signal 1 alone, raises the possibility that in vivo this chemokine serves to recruit activated T cells to become tolerant.

This article has been cited by other articles:

				T. Shin, G. Kennedy, K. Gorski, H. Tsuchiya, H. Koseki, M. Azuma, H. Yagita, L. Chen, J. Powell, D. Pardoll, et al. Cooperative B7-1/2 (CD80/CD86) and B7-DC Costimulation of CD4+ T Cells Independent of the PD-1 Receptor J. Exp. Med., July 7, 2003; 198(1): 31 - 38. [Abstract] [Full Text] [PDF]

				R. O. Williams Cutting Edge: A-Kinase Anchor Proteins Are Involved in Maintaining Resting T Cells in an Inactive State J. Immunol., June 1, 2002; 168(11): 5392 - 5396. [Abstract] [Full Text] [PDF]