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Development of CD8alpha/alpha and CD8alpha/beta T cells in major histocompatibility complex class I-deficient mice.

Das G, Janeway CA - J. Exp. Med. (1999)

Bottom Line: Peripheral CD8(+) T cells mainly use CD8alpha/beta, and their development is mainly dependent on the major histocompatibility complex (MHC) class I proteins K(b) and D(b) in H-2(b) mice.In this report, we have shown that the development of CD8alpha/beta TCR-alpha/beta cells in lymphoid organs as well as in intestinal intraepithelial lymphocytes (iIELs) is dependent on the MHC class I K(b) and D(b) proteins.In contrast, TCR-alpha/beta CD8alpha/alpha cells are found mainly in iIELs, and their numbers are unaffected in K(b)D(b) double knockout mice.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute and Yale University Medical School, New Haven, Connecticut 06510, USA.

ABSTRACT
Peripheral CD8(+) T cells mainly use CD8alpha/beta, and their development is mainly dependent on the major histocompatibility complex (MHC) class I proteins K(b) and D(b) in H-2(b) mice. In this report, we have shown that the development of CD8alpha/beta TCR-alpha/beta cells in lymphoid organs as well as in intestinal intraepithelial lymphocytes (iIELs) is dependent on the MHC class I K(b) and D(b) proteins. In contrast, TCR-alpha/beta CD8alpha/alpha cells are found mainly in iIELs, and their numbers are unaffected in K(b)D(b) double knockout mice. Most of the TCR-gamma/delta cells in the iIELs also bear CD8alpha/alpha, and they are also unaffected in K(b)D(b) -/- mice. In beta2-microglobulin (beta2m)-deficient mice, all of the TCR-alpha/beta CD8alpha/alpha and CD8alpha/beta T cells disappear, but TCR-gamma/delta cells are unaffected by the absence of beta2m.

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Composition of CD8α/α and CD8α/β T cells in different organs in KbDb double knockout mice. (a) Gating on TCR-α/β shows that in spleen, lymph node (LN), and liver, only a few CD8+ cells were found. In thymus and iIELs, a large number of CD8 cells were seen. They are CD8α/β+ in thymus and CD8α+CD8β− in iIELs. In staining of thymus cells (b), gating on TCR-α/β CD8α shows that all of the cells are CD8β+ as well. (c) Gating on TCR-α/β shows that only a few CD4−CD8α+ or CD4−CD8β+ cells are found. (d) In staining of iIELs gating on CD8α, there were large numbers of TCR-α/β and TCR-γ/δ cells.
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Figure 3: Composition of CD8α/α and CD8α/β T cells in different organs in KbDb double knockout mice. (a) Gating on TCR-α/β shows that in spleen, lymph node (LN), and liver, only a few CD8+ cells were found. In thymus and iIELs, a large number of CD8 cells were seen. They are CD8α/β+ in thymus and CD8α+CD8β− in iIELs. In staining of thymus cells (b), gating on TCR-α/β CD8α shows that all of the cells are CD8β+ as well. (c) Gating on TCR-α/β shows that only a few CD4−CD8α+ or CD4−CD8β+ cells are found. (d) In staining of iIELs gating on CD8α, there were large numbers of TCR-α/β and TCR-γ/δ cells.

Mentions: To evaluate the type of MHC restriction of both CD8α/α and CD8α/β T cells, we examined the composition of these two groups of cells in KbDb double knockout mice. It was found that most of the CD8α/β TCR-α/β cells disappeared in spleen, lymph node, and liver as well as in iIELs (Fig. 3 a). In iIELs, numbers of CD8α1 cells were not affected. In the thymus, there were normal numbers of CD4+CD8+ double positive (DP) cells in KbDb double knockout mice. These are presumed to be of the TCR-α/β lineage. However, there were virtually no CD4−CD8+ single positive (SP) cells (Fig. 3 c), and all of the DP cells were found to use CD8α/β (Fig. 3 b). Therefore, these DP cells in the thymus are uncommitted immature thymocytes that had not undergone intrathymic selection. Thus, CD8α/α1 T cells are mostly found in iIELs. This clearly indicates the potential for recognition of nonclassical MHC class Ib molecules by T cells bearing a TCR-α/β and the CD8α/α homodimer.


Development of CD8alpha/alpha and CD8alpha/beta T cells in major histocompatibility complex class I-deficient mice.

Das G, Janeway CA - J. Exp. Med. (1999)

Composition of CD8α/α and CD8α/β T cells in different organs in KbDb double knockout mice. (a) Gating on TCR-α/β shows that in spleen, lymph node (LN), and liver, only a few CD8+ cells were found. In thymus and iIELs, a large number of CD8 cells were seen. They are CD8α/β+ in thymus and CD8α+CD8β− in iIELs. In staining of thymus cells (b), gating on TCR-α/β CD8α shows that all of the cells are CD8β+ as well. (c) Gating on TCR-α/β shows that only a few CD4−CD8α+ or CD4−CD8β+ cells are found. (d) In staining of iIELs gating on CD8α, there were large numbers of TCR-α/β and TCR-γ/δ cells.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2195628&req=5

Figure 3: Composition of CD8α/α and CD8α/β T cells in different organs in KbDb double knockout mice. (a) Gating on TCR-α/β shows that in spleen, lymph node (LN), and liver, only a few CD8+ cells were found. In thymus and iIELs, a large number of CD8 cells were seen. They are CD8α/β+ in thymus and CD8α+CD8β− in iIELs. In staining of thymus cells (b), gating on TCR-α/β CD8α shows that all of the cells are CD8β+ as well. (c) Gating on TCR-α/β shows that only a few CD4−CD8α+ or CD4−CD8β+ cells are found. (d) In staining of iIELs gating on CD8α, there were large numbers of TCR-α/β and TCR-γ/δ cells.
Mentions: To evaluate the type of MHC restriction of both CD8α/α and CD8α/β T cells, we examined the composition of these two groups of cells in KbDb double knockout mice. It was found that most of the CD8α/β TCR-α/β cells disappeared in spleen, lymph node, and liver as well as in iIELs (Fig. 3 a). In iIELs, numbers of CD8α1 cells were not affected. In the thymus, there were normal numbers of CD4+CD8+ double positive (DP) cells in KbDb double knockout mice. These are presumed to be of the TCR-α/β lineage. However, there were virtually no CD4−CD8+ single positive (SP) cells (Fig. 3 c), and all of the DP cells were found to use CD8α/β (Fig. 3 b). Therefore, these DP cells in the thymus are uncommitted immature thymocytes that had not undergone intrathymic selection. Thus, CD8α/α1 T cells are mostly found in iIELs. This clearly indicates the potential for recognition of nonclassical MHC class Ib molecules by T cells bearing a TCR-α/β and the CD8α/α homodimer.

Bottom Line: Peripheral CD8(+) T cells mainly use CD8alpha/beta, and their development is mainly dependent on the major histocompatibility complex (MHC) class I proteins K(b) and D(b) in H-2(b) mice.In this report, we have shown that the development of CD8alpha/beta TCR-alpha/beta cells in lymphoid organs as well as in intestinal intraepithelial lymphocytes (iIELs) is dependent on the MHC class I K(b) and D(b) proteins.In contrast, TCR-alpha/beta CD8alpha/alpha cells are found mainly in iIELs, and their numbers are unaffected in K(b)D(b) double knockout mice.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute and Yale University Medical School, New Haven, Connecticut 06510, USA.

ABSTRACT
Peripheral CD8(+) T cells mainly use CD8alpha/beta, and their development is mainly dependent on the major histocompatibility complex (MHC) class I proteins K(b) and D(b) in H-2(b) mice. In this report, we have shown that the development of CD8alpha/beta TCR-alpha/beta cells in lymphoid organs as well as in intestinal intraepithelial lymphocytes (iIELs) is dependent on the MHC class I K(b) and D(b) proteins. In contrast, TCR-alpha/beta CD8alpha/alpha cells are found mainly in iIELs, and their numbers are unaffected in K(b)D(b) double knockout mice. Most of the TCR-gamma/delta cells in the iIELs also bear CD8alpha/alpha, and they are also unaffected in K(b)D(b) -/- mice. In beta2-microglobulin (beta2m)-deficient mice, all of the TCR-alpha/beta CD8alpha/alpha and CD8alpha/beta T cells disappear, but TCR-gamma/delta cells are unaffected by the absence of beta2m.

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Related in: MedlinePlus