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GENDER DEPENDENT IMMUNE REGULATION:
EFFECT OF REGULATORY T CELLS ON MACROPHAGES AND POTENTIAL
MECHANISM OF PROTECTION FROM AUTOIMMUNE DISEASE
by
Stefanie Johanna Kirwin
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR MICROBIOLOGY AND IMMUNOLOGY)
December 2006
Copyright 2006 Stefanie Johanna Kirwin
Object Description
| Title | Gender dependent immune regulation: effect of regulatory t cells on macrophages and potential mechanism of protection from autoimmune disease |
| Author | Kirwin, Stefanie Johanna |
| Author email | stefanie_kirwin@hotmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Microbiology & Immunology |
| School | Keck School of Medicine |
| Date defended/completed | 2006-10-19 |
| Date submitted | 2006 |
| Restricted until | Unrestricted |
| Date published | 2006-11-21 |
| Advisor (committee chair) | Tahara, Stanley M. |
| Advisor (committee member) |
Stohlman, Stephen Epstein, Alan L. Lai, Michael L. |
| Abstract | SJL mice exhibit a unique gender-dependent bias in their immune response. Males mount an anti-inflammatory Th2 response, whereas females react with an inflammatory Th1 response, which correlates with susceptibility to experimental autoimmune encephalomyelitis, a mouse model for multiple sclerosis. Castration as well as macrophage transfer from females reverses the male phenotype. Utilizing this mouse strain for the study of gender-dependent mechanisms of immune regulation, the role of CD25 regulatory T cells was examined. These cells maintain a Th2 environment in naïve males by regulating macrophage responsiveness. Transfer of macrophages from naïve CD25+-depleted males into untreated males results in a Th1 response after immunization demonstrating that regulatory T cells directly influence macrophage function. Males have a two-fold increase in the number of regulatory T cells compared to females, but no difference in cell surface marker expression or in vitro suppressive action was detected. The macrophage phenotype in naïve mice showed no difference in number or activation status comparing males and females. Analysis of cell surface molecules after antigen uptake uncovered a reduction in MHC class II expression on macrophages in males compared to females. The lack of antigen uptake by dendritic cells further confirmed the importance of a macrophage antigen presenting cell.; Male-derived Th2 cells suppress experimental autoimmune encephalomyelitis. Examination of the T cell response in protected mice showed only moderate reduction in CNS infiltrating cells and no difference in cell composition. However, MHC class II expression on microglia was significantly reduced indicating reduction in inflammatory cytokines such as IFN-[gamma]; and possible action of anti-inflammatory cytokines. Neither regulatory T cells nor Th2 cells were increased in the CNS of protected mice. However, selfantigen specific T cells in the CNS of protected mice demonstrated a shift in cytokine pattern from inflammatory Th1 to anti-inflammatory Th2. This suggests that the induction of a Th2 response to non-self antigen in the periphery can inhibit CNS inflammatory disease by altering the cytokine response to the potentially encephalitogenic selfantigen. |
| Keyword | autoimmunity; Th1/Th2; regulatory T cells; macrophage; multiple sclerosis |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m182 |
| Contributing entity | University of Southern California |
| Rights | Kirwin, Stefanie Johanna |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@dots.usc.edu |
| Filename | etd-Kirwin-20061121 |
| Archival file | uscthesesreloadpub_Volume14/etd-Kirwin-20061121.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | GENDER DEPENDENT IMMUNE REGULATION: EFFECT OF REGULATORY T CELLS ON MACROPHAGES AND POTENTIAL MECHANISM OF PROTECTION FROM AUTOIMMUNE DISEASE by Stefanie Johanna Kirwin A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (MOLECULAR MICROBIOLOGY AND IMMUNOLOGY) December 2006 Copyright 2006 Stefanie Johanna Kirwin |
