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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baumgart, M. Articles by Hesse, M. Search for Related Content PubMed PubMed Citation Articles by Baumgart, M. Articles by Hesse, M.

Naturally Occurring CD4⁺Foxp3⁺ Regulatory T Cells Are an Essential, IL-10-Independent Part of the Immunoregulatory Network in Schistosoma mansoni Egg-Induced Inflammation

Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY, 14853

In acute and chronic schistosomiasis, survival of the host requires a carefully balanced immune response against highly immunogenic parasite eggs. We characterized the phenotype, distribution, and functional role of CD4⁺Foxp3⁺ naturally occurring regulatory T cells (naTregs) in schistosome egg-induced inflammation. In adoptive transfer experiments and by intracellular staining for Foxp3, we demonstrate significant frequencies of naTregs in hepatic granulomas and draining lymphoid tissues of mice infected with the trematode Schistosoma mansoni. Strikingly, egg-induced inflammation does not change the normal ratio between naTregs and effector CD4⁺ T cells at the inflammatory site or in lymphoid organs in acute or chronic disease. However, increasing frequencies of CD103-expressing cells in the naTreg compartment indicate a change in phenotype for naTregs with disease progression. Because CD103 was described recently as an activation marker for naTregs, we speculate that naTregs in chronic schistosomiasis are potentially more suppressive. Furthermore, we found that most naTregs do not contribute to egg-induced IL-4 and IL-10 production. Importantly, depletion of CD25⁺ naTregs strongly enhances the frequency of IL-4-producing effector T cells in acute egg-induced inflammation. It does not change clonal expansion of activated CD4⁺ T cells. This regulation of egg-induced cytokine production does not require the presence of IL-10. These data demonstrate that naTregs limit egg-induced effector-cytokine production in our model. Our results identify naTregs as an important, IL-10-independent part of the regulatory network in schistosome egg-induced inflammation.

This article has been cited by other articles:

				S. Rausch, J. Huehn, D. Kirchhoff, J. Rzepecka, C. Schnoeller, S. Pillai, C. Loddenkemper, A. Scheffold, A. Hamann, R. Lucius, et al. Functional Analysis of Effector and Regulatory T Cells in a Parasitic Nematode Infection Infect. Immun., May 1, 2008; 76(5): 1908 - 1919. [Abstract] [Full Text] [PDF]

				C. Schnoeller, S. Rausch, S. Pillai, A. Avagyan, B. M. Wittig, C. Loddenkemper, A. Hamann, E. Hamelmann, R. Lucius, and S. Hartmann A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages J. Immunol., March 15, 2008; 180(6): 4265 - 4272. [Abstract] [Full Text] [PDF]

				C. Siewert, U. Lauer, S. Cording, T. Bopp, E. Schmitt, A. Hamann, and J. Huehn Experience-Driven Development: Effector/Memory-Like {alpha}E+Foxp3+ Regulatory T Cells Originate from Both Naive T Cells and Naturally Occurring Naive-Like Regulatory T Cells J. Immunol., January 1, 2008; 180(1): 146 - 155. [Abstract] [Full Text] [PDF]

				K. Watanabe, P. N. M. Mwinzi, C. L. Black, E. M. O. Muok, D. M. S. Karanja, W. E. Secor, and D. G. Colley T Regulatory Cell Levels Decrease in People Infected With Schistosoma mansoni on Effective Treatment Am J Trop Med Hyg, October 1, 2007; 77(4): 676 - 682. [Abstract] [Full Text] [PDF]

				S. J. Jenkins, G. Perona-Wright, A. G. F. Worsley, N. Ishii, and A. S. MacDonald Dendritic Cell Expression of OX40 Ligand Acts as a Costimulatory, Not Polarizing, Signal for Optimal Th2 Priming and Memory Induction In Vivo J. Immunol., September 15, 2007; 179(6): 3515 - 3523. [Abstract] [Full Text] [PDF]

				M. Guilliams, G. Oldenhove, W. Noel, M. Herin, L. Brys, P. Loi, V. Flamand, M. Moser, P. De Baetselier, and A. Beschin African Trypanosomiasis: Naturally Occurring Regulatory T Cells Favor Trypanotolerance by Limiting Pathology Associated with Sustained Type 1 Inflammation J. Immunol., September 1, 2007; 179(5): 2748 - 2757. [Abstract] [Full Text] [PDF]

				H. Nagase, K. M. Jones, C. F. Anderson, and N. Noben-Trauth Despite Increased CD4+Foxp3+ Cells within the Infection Site, BALB/c IL-4 Receptor-Deficient Mice Reveal CD4+Foxp3-Negative T Cells as a Source of IL-10 in Leishmania major Susceptibility J. Immunol., August 15, 2007; 179(4): 2435 - 2444. [Abstract] [Full Text] [PDF]

				D. P. Beiting, L. F. Gagliardo, M. Hesse, S. K. Bliss, D. Meskill, and J. A. Appleton Coordinated Control of Immunity to Muscle Stage Trichinella spiralis by IL-10, Regulatory T Cells, and TGF-beta J. Immunol., January 15, 2007; 178(2): 1039 - 1047. [Abstract] [Full Text] [PDF]

				K. A. Cavassani, A. P. Campanelli, A. P. Moreira, J. O. Vancim, L. H. Vitali, R. C. Mamede, R. Martinez, and J. S. Silva Systemic and Local Characterization of Regulatory T Cells in a Chronic Fungal Infection in Humans J. Immunol., November 1, 2006; 177(9): 5811 - 5818. [Abstract] [Full Text] [PDF]