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CD4+ cell tolerance to self and feta...
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Lerman, Melissa Ann.
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CD4+ cell tolerance to self and fetal HA.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
CD4+ cell tolerance to self and fetal HA./
作者:
Lerman, Melissa Ann.
面頁冊數:
224 p.
附註:
Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1233.
Contained By:
Dissertation Abstracts International65-03B.
標題:
Health Sciences, Immunology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3125855
ISBN:
0496731440
CD4+ cell tolerance to self and fetal HA.
Lerman, Melissa Ann.
CD4+ cell tolerance to self and fetal HA.
- 224 p.
Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1233.
Thesis (Ph.D.)--University of Pennsylvania, 2004.
To better understand immune tolerance to class-II restricted antigens, we investigated T cell tolerance to a single peptide antigen when it was expressed both as a self-antigen and as a fetal-antigen. First, we examined the development of self-peptide-specific CD4+ T cells in lineages of transgenic mice that express the influenza virus PR8 hemagglutinin (HA) under the control of several different promoters. By mating these lineages with TS1 transgenic mice that express a T cell receptor that recognizes the major I-Ed -restricted determinant from HA (S1) we demonstrated that neo-self antigen-specific T cells undergo selection to become CD4+ CD25 + regulatory T cells in each of the lineages, although in varying numbers. Interestingly, even though their numbers varied in the different lineages, in all cases S1-specific CD4+ CD25+ regulatory T cells coexisted with similar numbers of clonally-related CD4 + CD25- T cells which lacked regulatory function. Thus, CD4+ CD25+ T cells directed towards known self-antigens were generated as a part of normal T cell development. While radioresistant stromal cells consistently directed both deletion and CD25 + T cell selection of S1-specific thymocytes, BM-derived cells also contributed to CD25+ T cell development. Second, in order to investigate how mothers maintain fetuses carrying foreign paternal antigens, we explored the ability of pregnant females to mount class-II restricted responses. BALB/c females were mated with HA-expressing males, and S1-specific T cells were adoptively transferred into the mothers. Surprisingly, these cells responded to paternally-derived fetal antigen. However, responses were restricted to the para-aortic lymph nodes (LN), demonstrating both that the para-aortic LN are uniquely exposed to fetal antigen and that the maternal immune system can respond to fetal antigens. Moreover, in the para-aortic LN, T cell proliferation to self-antigens was decreased from that in all other LN, demonstrating that T cell responsiveness may be modulated specifically in those LN exposed to fetal antigen. Interestingly then, we demonstrate that T cell tolerance can be mediated through the generation of CD25+ T cells as well as through other mechanisms that restrict T cell proliferation in vivo.
ISBN: 0496731440Subjects--Topical Terms:
1017716
Health Sciences, Immunology.
CD4+ cell tolerance to self and fetal HA.
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To better understand immune tolerance to class-II restricted antigens, we investigated T cell tolerance to a single peptide antigen when it was expressed both as a self-antigen and as a fetal-antigen. First, we examined the development of self-peptide-specific CD4+ T cells in lineages of transgenic mice that express the influenza virus PR8 hemagglutinin (HA) under the control of several different promoters. By mating these lineages with TS1 transgenic mice that express a T cell receptor that recognizes the major I-Ed -restricted determinant from HA (S1) we demonstrated that neo-self antigen-specific T cells undergo selection to become CD4+ CD25 + regulatory T cells in each of the lineages, although in varying numbers. Interestingly, even though their numbers varied in the different lineages, in all cases S1-specific CD4+ CD25+ regulatory T cells coexisted with similar numbers of clonally-related CD4 + CD25- T cells which lacked regulatory function. Thus, CD4+ CD25+ T cells directed towards known self-antigens were generated as a part of normal T cell development. While radioresistant stromal cells consistently directed both deletion and CD25 + T cell selection of S1-specific thymocytes, BM-derived cells also contributed to CD25+ T cell development. Second, in order to investigate how mothers maintain fetuses carrying foreign paternal antigens, we explored the ability of pregnant females to mount class-II restricted responses. BALB/c females were mated with HA-expressing males, and S1-specific T cells were adoptively transferred into the mothers. Surprisingly, these cells responded to paternally-derived fetal antigen. However, responses were restricted to the para-aortic lymph nodes (LN), demonstrating both that the para-aortic LN are uniquely exposed to fetal antigen and that the maternal immune system can respond to fetal antigens. Moreover, in the para-aortic LN, T cell proliferation to self-antigens was decreased from that in all other LN, demonstrating that T cell responsiveness may be modulated specifically in those LN exposed to fetal antigen. Interestingly then, we demonstrate that T cell tolerance can be mediated through the generation of CD25+ T cells as well as through other mechanisms that restrict T cell proliferation in vivo.
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