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

Published online before print June 22, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.1205719v1 80/3/538    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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takase, H. Articles by Gery, I. Search for Related Content PubMed PubMed Citation Articles by Takase, H. Articles by Gery, I.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1205719

Received for publication December 8, 2005.
Revised April 25, 2006.
Accepted for publication May 7, 2006.

Article

Inflammatory processes triggered by TCR engagement or by local cytokine expression: differences in profiles of gene expression and infiltrating cell populations

Hiroshi Takase ^*, Cheng-Rong Yu ^*, Don-Il Ham ^*, Chi-Chao Chan ^*, Jun Chen ^*, Barbara P. Vistica ^*, Eric F. Wawrousek , Scott K. Durum , Charles E. Egwuagu ^*, and Igal Gery ^*@

Laboratories of *Immunology and Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland; Laboratory of Molecular Immunoregulation, National Cancer Institute, National Institutes of Health, Frederick, Maryland; and Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School, Japan

^@ To whom correspondence should be addressed. E-mail: geryi{at}nei.nih.gov.

	Abstract

Immune cell-mediated inflammatory responses are triggered by T cell receptor (TCR) engagement with the target antigen, the initial event that brings about the complex sequence of events of the inflammatory process. Another form of inflammation is induced by local expression of certain cytokines. Unlike the former form of inflammation, little is known about the basic features of the cytokine-induced responses. Here, we analyzed tissue morphology, the infiltrating cells, and up-regulated, inflammation-related genes in mouse eyes in which inflammation is triggered by local transgenic (Tg) expression of cytokines and compared these features with those in eyes with experimental autoimmune uveitis (EAU), in which inflammation is initiated by engagement of TCR on sensitized T cells with their target antigen, followed by the well-defined, subsequent cytokine production. Eyes of interferon (IFN)- Tg mice exhibited severe, morphological changes but essentially no inflammation, and intense inflammation was found in eyes of interleukin (IL)-1 or IL-7 Tg mice. The cellular infiltration in eyes of these latter two lines of Tg mice resembled that in eyes with EAU by including many CD4 cells, but unlike in EAU, the infiltration in Tg eyes contained large proportions of B cells and only small numbers of macrophages. Real-time polymerase chain reaction analysis of eye RNA revealed differences among the disease models in the expression profiles of various inflammation-related genes. It is interesting that a bias toward T helper cell type 1 immunity (high IFN-, regulated on activation, normal T expressed and secreted/CC chemokine ligand 5, monokine induced by IFN-/CXC chemokine ligand 9, and T-bet but low IL-4, IL-5, and GATA-3 transcripts) was found in EAU eyes but not in eyes of IL-1 and IL-7 Tg mice. The results thus show that similar to TCR engagement, local expression of certain cytokines triggers a complex, subsequent production of numerous inflammation-related molecules, but features of the ensued inflammatory process are determined by the triggering mechanism.

Key Words: immune-mediated inflammation • eye • experimental autoimmune uveitis (EAU) • transgenic mice

This article has been cited by other articles:

				G. Shi, A. Maminishkis, T. Banzon, S. Jalickee, R. Li, J. Hammer, and S. S. Miller Control of Chemokine Gradients by the Retinal Pigment Epithelium Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4620 - 4630. [Abstract] [Full Text] [PDF]