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 Rutitzky, L. I. Articles by Stadecker, M. J. Search for Related Content PubMed PubMed Citation Articles by Rutitzky, L. I. Articles by Stadecker, M. J. Pubmed/NCBI databases Substance via MeSH

Apoptosis by Neglect of CD4⁺ Th Cells in Granulomas: A Novel Effector Mechanism Involved in the Control of Egg-Induced Immunopathology in Murine Schistosomiasis¹

Department of Pathology, Tufts University School of Medicine, Boston, MA 02111

In infection with Schistosoma mansoni, parasite eggs precipitate an intrahepatic granulomatous and fibrosing inflammation that is mediated by CD4⁺ Th cells. Compared with CBA mice, C57BL/6 mice develop smaller granulomas composed of cells that exhibit reduced proliferative responses to schistosome egg Ags. In the present study, we investigated CD4⁺ T cell apoptosis as a possible mechanism that could account for this subdued response. We found throughout the course of several infection weeks a markedly higher proportion of apoptotic CD4⁺ T cells in granulomas from C57BL/6 mice than in those from CBA mice ex vivo; the apoptosis further increased upon cell cultivation in vitro. Activation-induced cell death or CD8⁺ T cells failed to account for the enhanced apoptosis as infected Fas-, Fas ligand,- and CD8-deficient mice exhibited similar apoptosis to that seen in wild-type counterparts. However, a strikingly lower IL-2 production by schistosome egg Ag-stimulated C57BL/6 granuloma and mesenteric lymph node cells suggested the possibility of apoptosis due to growth factor deprivation. Indeed, the CD4⁺ T cell apoptosis was significantly reversed by addition of rIL-2 in vitro, or by injection of rIL-2 in vivo, which also resulted in significant exacerbation of granulomatous inflammation. These findings indicate that apoptosis by neglect can represent a significant means of controlling CD4⁺ T cells that mediate the immunopathology in schistosomiasis.

This article has been cited by other articles:

				M. G. Shainheit, P. M. Smith, L. E. Bazzone, A. C. Wang, L. I. Rutitzky, and M. J. Stadecker Dendritic Cell IL-23 and IL-1 Production in Response to Schistosome Eggs Induces Th17 Cells in a Mouse Strain Prone to Severe Immunopathology J. Immunol., December 15, 2008; 181(12): 8559 - 8567. [Abstract] [Full Text] [PDF]

				L. I. Rutitzky, L. Bazzone, M. G. Shainheit, B. Joyce-Shaikh, D. J. Cua, and M. J. Stadecker IL-23 Is Required for the Development of Severe Egg-Induced Immunopathology in Schistosomiasis and for Lesional Expression of IL-17 J. Immunol., February 15, 2008; 180(4): 2486 - 2495. [Abstract] [Full Text] [PDF]

				M. Baumgart, F. Tompkins, J. Leng, and M. Hesse Naturally Occurring CD4+Foxp3+ Regulatory T Cells Are an Essential, IL-10-Independent Part of the Immunoregulatory Network in Schistosoma mansoni Egg-Induced Inflammation J. Immunol., May 1, 2006; 176(9): 5374 - 5387. [Abstract] [Full Text] [PDF]

				L. I. Rutitzky, J. R. Lopes da Rosa, and M. J. Stadecker Severe CD4 T Cell-Mediated Immunopathology in Murine Schistosomiasis Is Dependent on IL-12p40 and Correlates with High Levels of IL-17 J. Immunol., September 15, 2005; 175(6): 3920 - 3926. [Abstract] [Full Text] [PDF]

				L. I. Rutitzky, H. J. Hernandez, Y.-S. Yim, D. E. Ricklan, E. Finger, C. Mohan, I. Peter, E. K. Wakeland, and M. J. Stadecker Enhanced Egg-Induced Immunopathology Correlates With High IFN-{gamma} in Murine Schistosomiasis: Identification of Two Epistatic Genetic Intervals J. Immunol., January 1, 2005; 174(1): 435 - 440. [Abstract] [Full Text] [PDF]