Memory/effector T cells in TCR transgenic mice develop via recognition of enteric antigens by a second, endogenous TCR

Arman Saparov, Lisa A. Kraus, Yingzi Cong, Jeff Marwill, Xiao Yan Xu, Charles O. Elson, Casey T. Weaver

Research output: Contribution to journalArticle

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Abstract

The majority of clonotypic CD4+ T cells in the intestinal lamina propria of DO11.10 TCR transgenic mice have an activated/memory phenotype and produce effector cytokines despite the absence of prior exposure to ovalbumin (OVA), the transgene-specific antigen. A small number of splenic T cells have a similar phenotype. Clonotypic T cells from Peyer's patch are intermediate in both phenotype and effector cytokine production. Flow cytometric analysis of cells isolated from thymectomized, OVA-naive DO11.10 mice treated with continuous administration of BrdU indicated that a significant fraction of clonotype-positive T cells in the lamina propria and Peyer's patch were in the cell cycle, with significantly fewer cycling cells in the spleen. Most of the cycling cells from each anatomic site expressed low levels of CD45RB. Effector cytokine expression was enriched in the CD45RB(low) populations. These memory/effector cell populations were eliminated in DO11.10/SCID and DO11.10/RAG-2(-/-) mice, suggesting that recognition of non-OVA antigens through a second, non-clonotypic TCR was driving differentiation of memory/effector cells in naive BALB/c DO11.10 mice. Clonotypic CD4+ T cells isolated from DO11.10, but not from DO11.10/SCID or DO11.10/RAG-2(-/-) mice, were stimulated to enter the cell cycle by antigen-presenting cells pulsed with an intestinal bacterial antigen extract. These data provide direct evidence that enteric bacterial antigens can activate transgenic T cells through a second, non-clonotypic TCR, and support the notion that the development and turnover of memory/effector cells in vivo is driven by the intestinal flora.

LanguageEnglish
Pages1253-1263
Number of pages11
JournalInternational Immunology
Volume11
Issue number8
DOIs
StatePublished - 1999
Externally publishedYes

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Transgenic Mice
T-Lymphocytes
Antigens
Bacterial Antigens
Peyer's Patches
Ovalbumin
Cytokines
Phenotype
Cell Cycle
Mucous Membrane
Antigen-Presenting Cells
Bromodeoxyuridine
Transgenes
Population
Recognition (Psychology)
Spleen

Keywords

  • CD4 T cell
  • Cytokines
  • In situ hybridization
  • Mucosal immunity
  • T cell memory
  • TCR transgenic mice

ASJC Scopus subject areas

  • Immunology

Cite this

Memory/effector T cells in TCR transgenic mice develop via recognition of enteric antigens by a second, endogenous TCR. / Saparov, Arman; Kraus, Lisa A.; Cong, Yingzi; Marwill, Jeff; Xu, Xiao Yan; Elson, Charles O.; Weaver, Casey T.

In: International Immunology, Vol. 11, No. 8, 1999, p. 1253-1263.

Research output: Contribution to journalArticle

Saparov, Arman ; Kraus, Lisa A. ; Cong, Yingzi ; Marwill, Jeff ; Xu, Xiao Yan ; Elson, Charles O. ; Weaver, Casey T./ Memory/effector T cells in TCR transgenic mice develop via recognition of enteric antigens by a second, endogenous TCR. In: International Immunology. 1999 ; Vol. 11, No. 8. pp. 1253-1263
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abstract = "The majority of clonotypic CD4+ T cells in the intestinal lamina propria of DO11.10 TCR transgenic mice have an activated/memory phenotype and produce effector cytokines despite the absence of prior exposure to ovalbumin (OVA), the transgene-specific antigen. A small number of splenic T cells have a similar phenotype. Clonotypic T cells from Peyer's patch are intermediate in both phenotype and effector cytokine production. Flow cytometric analysis of cells isolated from thymectomized, OVA-naive DO11.10 mice treated with continuous administration of BrdU indicated that a significant fraction of clonotype-positive T cells in the lamina propria and Peyer's patch were in the cell cycle, with significantly fewer cycling cells in the spleen. Most of the cycling cells from each anatomic site expressed low levels of CD45RB. Effector cytokine expression was enriched in the CD45RB(low) populations. These memory/effector cell populations were eliminated in DO11.10/SCID and DO11.10/RAG-2(-/-) mice, suggesting that recognition of non-OVA antigens through a second, non-clonotypic TCR was driving differentiation of memory/effector cells in naive BALB/c DO11.10 mice. Clonotypic CD4+ T cells isolated from DO11.10, but not from DO11.10/SCID or DO11.10/RAG-2(-/-) mice, were stimulated to enter the cell cycle by antigen-presenting cells pulsed with an intestinal bacterial antigen extract. These data provide direct evidence that enteric bacterial antigens can activate transgenic T cells through a second, non-clonotypic TCR, and support the notion that the development and turnover of memory/effector cells in vivo is driven by the intestinal flora.",
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AU - Kraus,Lisa A.

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AU - Xu,Xiao Yan

AU - Elson,Charles O.

AU - Weaver,Casey T.

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KW - In situ hybridization

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