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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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Male-reactive cells undergoing apoptosis preferentially associate with cortical DCs. (A) Immunofluorescence staining for CD11c in the thymus. Areas of cortex and medulla are indicated. Bar, 250 μm. (B) Thymus tissue sections from mice in Figs. 3 and 5 were analyzed by immunofluorescence for Thy1.2, active Caspase 3, and CD11c. A Thy1.2 and active Caspase 3+ colocalized cell immediately adjacent to a CD11c+ cell is indicated by arrows. Bar, 5 μm. (C) The frequency of cells associated with CD11c+ cells was quantified for the indicated subsets. Data represent the mean from four different males ± SD. P < 0.0001. The frequency of cells associated with F4/80+ cells is also depicted. Data are representative of two individual groups of chimeras and one set of immunofluorescence staining.
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fig7: Male-reactive cells undergoing apoptosis preferentially associate with cortical DCs. (A) Immunofluorescence staining for CD11c in the thymus. Areas of cortex and medulla are indicated. Bar, 250 μm. (B) Thymus tissue sections from mice in Figs. 3 and 5 were analyzed by immunofluorescence for Thy1.2, active Caspase 3, and CD11c. A Thy1.2 and active Caspase 3+ colocalized cell immediately adjacent to a CD11c+ cell is indicated by arrows. Bar, 5 μm. (C) The frequency of cells associated with CD11c+ cells was quantified for the indicated subsets. Data represent the mean from four different males ± SD. P < 0.0001. The frequency of cells associated with F4/80+ cells is also depicted. Data are representative of two individual groups of chimeras and one set of immunofluorescence staining.

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)

Male-reactive cells undergoing apoptosis preferentially associate with cortical DCs. (A) Immunofluorescence staining for CD11c in the thymus. Areas of cortex and medulla are indicated. Bar, 250 μm. (B) Thymus tissue sections from mice in Figs. 3 and 5 were analyzed by immunofluorescence for Thy1.2, active Caspase 3, and CD11c. A Thy1.2 and active Caspase 3+ colocalized cell immediately adjacent to a CD11c+ cell is indicated by arrows. Bar, 5 μm. (C) The frequency of cells associated with CD11c+ cells was quantified for the indicated subsets. Data represent the mean from four different males ± SD. P < 0.0001. The frequency of cells associated with F4/80+ cells is also depicted. Data are representative of two individual groups of chimeras and one set of immunofluorescence staining.
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Male-reactive cells undergoing apoptosis preferentially associate with cortical DCs. (A) Immunofluorescence staining for CD11c in the thymus. Areas of cortex and medulla are indicated. Bar, 250 μm. (B) Thymus tissue sections from mice in Figs. 3 and 5 were analyzed by immunofluorescence for Thy1.2, active Caspase 3, and CD11c. A Thy1.2 and active Caspase 3+ colocalized cell immediately adjacent to a CD11c+ cell is indicated by arrows. Bar, 5 μm. (C) The frequency of cells associated with CD11c+ cells was quantified for the indicated subsets. Data represent the mean from four different males ± SD. P < 0.0001. The frequency of cells associated with F4/80+ cells is also depicted. Data are representative of two individual groups of chimeras and one set of immunofluorescence staining.
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