Limits...
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.

Show MeSH

Related in: MedlinePlus

Cortical DCs are efficient APC for inducing clonal deletion. Female HYcd4 Dbo BM was mixed with nontransgenic Dbo BM or CD11c-DTR female BM and transferred into Dbo or WT female recipients, respectively, as controls. Female HYcd4 Dbo BM was also mixed with male CD11c-DTR BM and transferred into WT females or males and either left untreated or treated with DTx. Activation of Caspase 3 in treated versus untreated T3.70+ thymocytes of the indicated group is depicted. Data represent the mean from three to five mice ± SD. The fold change comparing untreated and DTx-treated mice for each group is indicated. P < 0.0001 for the male into female group and P = 0.0242 for the male into male group. ND, not done. Data are representative of four separate experiments.
© Copyright Policy
Related In: Results  -  Collection

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

fig8: Cortical DCs are efficient APC for inducing clonal deletion. Female HYcd4 Dbo BM was mixed with nontransgenic Dbo BM or CD11c-DTR female BM and transferred into Dbo or WT female recipients, respectively, as controls. Female HYcd4 Dbo BM was also mixed with male CD11c-DTR BM and transferred into WT females or males and either left untreated or treated with DTx. Activation of Caspase 3 in treated versus untreated T3.70+ thymocytes of the indicated group is depicted. Data represent the mean from three to five mice ± SD. The fold change comparing untreated and DTx-treated mice for each group is indicated. P < 0.0001 for the male into female group and P = 0.0242 for the male into male group. ND, not done. Data are representative of four separate experiments.

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)

Cortical DCs are efficient APC for inducing clonal deletion. Female HYcd4 Dbo BM was mixed with nontransgenic Dbo BM or CD11c-DTR female BM and transferred into Dbo or WT female recipients, respectively, as controls. Female HYcd4 Dbo BM was also mixed with male CD11c-DTR BM and transferred into WT females or males and either left untreated or treated with DTx. Activation of Caspase 3 in treated versus untreated T3.70+ thymocytes of the indicated group is depicted. Data represent the mean from three to five mice ± SD. The fold change comparing untreated and DTx-treated mice for each group is indicated. P < 0.0001 for the male into female group and P = 0.0242 for the male into male group. ND, not done. Data are representative of four separate experiments.
© Copyright Policy
Related In: Results  -  Collection

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

fig8: Cortical DCs are efficient APC for inducing clonal deletion. Female HYcd4 Dbo BM was mixed with nontransgenic Dbo BM or CD11c-DTR female BM and transferred into Dbo or WT female recipients, respectively, as controls. Female HYcd4 Dbo BM was also mixed with male CD11c-DTR BM and transferred into WT females or males and either left untreated or treated with DTx. Activation of Caspase 3 in treated versus untreated T3.70+ thymocytes of the indicated group is depicted. Data represent the mean from three to five mice ± SD. The fold change comparing untreated and DTx-treated mice for each group is indicated. P < 0.0001 for the male into female group and P = 0.0242 for the male into male group. ND, not done. Data are representative of four separate experiments.
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
Related in: MedlinePlus