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Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla.

McCaughtry TM, Baldwin TA, Wilken MS, Hogquist KA - J. Exp. Med. (2008)

Bottom Line: However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation.We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation.Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion.

View Article: PubMed Central - PubMed

Affiliation: Center for Immunology, Laboratory Medicine, and Pathology, University of Minnesota, Minneapolis, MN 55454, USA.

ABSTRACT
The thymic medulla is generally held to be a specialized environment for negative selection. However, many self-reactive thymocytes first encounter ubiquitous self-antigens in the cortex. Cortical epithelial cells are vital for positive selection, but whether such cells can also promote negative selection is controversial. We used the HY(cd4) model, where T cell receptor for antigen (TCR) expression is appropriately timed and a ubiquitous self-antigen drives clonal deletion in male mice. We demonstrated unambiguously that this deletion event occurs in the thymic cortex. However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation. We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation. Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion.

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Radioresistant cells and cortical epithelial cells inefficiently induce apoptosis. HYcd4 Dbo female BM was mixed with female or male BM from WT mice and transferred into WT female and male recipients as controls. (A) A cohort of WT male mice reconstituted with a mixture of HYcd4 Dbo female BM and nontransgenic Dbo female BM was added. Data are representative of two separate experiments. (B) A cohort of female mice expressing the K14-HYp transgene reconstituted with a mixture of HYcd4 Dbo BM and WT female BM was added. Data are representative of five separate experiments. The frequency of active Caspase 3+ T3.70+ cells in chimeric mice is shown. Data represent the mean from three to six individuals ± SD. Fold change over the female control group is indicated. A, P = 0.0463 when comparing the male radioresistant group to the WT female group and P = 0.1191 when comparing the male radioresistant group to the WT male group; B, P = 0.0042 when comparing WT male and female groups and P = 0.0085 when comparing the WT male group to the female K14-HYp group.
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fig6: Radioresistant cells and cortical epithelial cells inefficiently induce apoptosis. HYcd4 Dbo female BM was mixed with female or male BM from WT mice and transferred into WT female and male recipients as controls. (A) A cohort of WT male mice reconstituted with a mixture of HYcd4 Dbo female BM and nontransgenic Dbo female BM was added. Data are representative of two separate experiments. (B) A cohort of female mice expressing the K14-HYp transgene reconstituted with a mixture of HYcd4 Dbo BM and WT female BM was added. Data are representative of five separate experiments. The frequency of active Caspase 3+ T3.70+ cells in chimeric mice is shown. Data represent the mean from three to six individuals ± SD. Fold change over the female control group is indicated. A, P = 0.0463 when comparing the male radioresistant group to the WT female group and P = 0.1191 when comparing the male radioresistant group to the WT male group; B, P = 0.0042 when comparing WT male and female groups and P = 0.0085 when comparing the WT male group to the female K14-HYp group.

Mentions: A summary of mixed BM chimeras generated for these studies


Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla.

McCaughtry TM, Baldwin TA, Wilken MS, Hogquist KA - J. Exp. Med. (2008)

Radioresistant cells and cortical epithelial cells inefficiently induce apoptosis. HYcd4 Dbo female BM was mixed with female or male BM from WT mice and transferred into WT female and male recipients as controls. (A) A cohort of WT male mice reconstituted with a mixture of HYcd4 Dbo female BM and nontransgenic Dbo female BM was added. Data are representative of two separate experiments. (B) A cohort of female mice expressing the K14-HYp transgene reconstituted with a mixture of HYcd4 Dbo BM and WT female BM was added. Data are representative of five separate experiments. The frequency of active Caspase 3+ T3.70+ cells in chimeric mice is shown. Data represent the mean from three to six individuals ± SD. Fold change over the female control group is indicated. A, P = 0.0463 when comparing the male radioresistant group to the WT female group and P = 0.1191 when comparing the male radioresistant group to the WT male group; B, P = 0.0042 when comparing WT male and female groups and P = 0.0085 when comparing the WT male group to the female K14-HYp group.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2571932&req=5

fig6: Radioresistant cells and cortical epithelial cells inefficiently induce apoptosis. HYcd4 Dbo female BM was mixed with female or male BM from WT mice and transferred into WT female and male recipients as controls. (A) A cohort of WT male mice reconstituted with a mixture of HYcd4 Dbo female BM and nontransgenic Dbo female BM was added. Data are representative of two separate experiments. (B) A cohort of female mice expressing the K14-HYp transgene reconstituted with a mixture of HYcd4 Dbo BM and WT female BM was added. Data are representative of five separate experiments. The frequency of active Caspase 3+ T3.70+ cells in chimeric mice is shown. Data represent the mean from three to six individuals ± SD. Fold change over the female control group is indicated. A, P = 0.0463 when comparing the male radioresistant group to the WT female group and P = 0.1191 when comparing the male radioresistant group to the WT male group; B, P = 0.0042 when comparing WT male and female groups and P = 0.0085 when comparing the WT male group to the female K14-HYp group.
Mentions: A summary of mixed BM chimeras generated for these studies

Bottom Line: However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation.We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation.Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion.

View Article: PubMed Central - PubMed

Affiliation: Center for Immunology, Laboratory Medicine, and Pathology, University of Minnesota, Minneapolis, MN 55454, USA.

ABSTRACT
The thymic medulla is generally held to be a specialized environment for negative selection. However, many self-reactive thymocytes first encounter ubiquitous self-antigens in the cortex. Cortical epithelial cells are vital for positive selection, but whether such cells can also promote negative selection is controversial. We used the HY(cd4) model, where T cell receptor for antigen (TCR) expression is appropriately timed and a ubiquitous self-antigen drives clonal deletion in male mice. We demonstrated unambiguously that this deletion event occurs in the thymic cortex. However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation. We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation. Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion.

Show MeSH