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Generation of PLZF+ CD4+ T cells via MHC class II-dependent thymocyte-thymocyte interaction is a physiological process in humans.

Lee YJ, Jeon YK, Kang BH, Chung DH, Park CG, Shin HY, Jung KC, Park SH - J. Exp. Med. (2009)

Bottom Line: However, the developmental dissection of this T-T interaction in humans has not been possible because of the lack of known cellular molecules specific for T-T CD4+ T cells.Although these characteristics are quite similar to invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have a diverse T cell receptor repertoire and are restricted by MHC class II molecules.These findings define a novel human CD4+ T cell subset that develops via an MHC class II-dependent T-T interaction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.

ABSTRACT
Human thymocytes, unlike mouse thymocytes, express major histocompatibility complex (MHC) class II molecules on their surface, especially during the fetal and perinatal stages. Based on this observation, we previously identified a novel developmental pathway for the generation of CD4+ T cells via interactions between MHC class II-expressing thymocytes (thymocyte-thymocyte [T-T] interactions) with a transgenic mouse system. However, the developmental dissection of this T-T interaction in humans has not been possible because of the lack of known cellular molecules specific for T-T CD4+ T cells. We show that promyelocytic leukemia zinc finger protein (PLZF) is a useful marker for the identification of T-T CD4+ T cells. With this analysis, we determined that a substantial number of fetal thymocytes and splenocytes express PLZF and acquire innate characteristics during their development in humans. Although these characteristics are quite similar to invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have a diverse T cell receptor repertoire and are restricted by MHC class II molecules. These findings define a novel human CD4+ T cell subset that develops via an MHC class II-dependent T-T interaction.

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PLZF+ T–T CD4+ T cells in mice and humans have diverse TCR Vβ usage. The bar graph shows the Vβ chain distribution of PLZF+ and PLZF− CD4 SP thymocytes and splenic CD4+ T cells from CIITAtgpIV−/− mice (A) and a human fetus (GA = 18 wk; B). This is compared with conventional CD4+ T cells from a WT mouse (A) and human cord blood (B). The data are mean values ± SEM of four animals in each group of mice, with one human fetus and four cord blood samples.
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fig4: PLZF+ T–T CD4+ T cells in mice and humans have diverse TCR Vβ usage. The bar graph shows the Vβ chain distribution of PLZF+ and PLZF− CD4 SP thymocytes and splenic CD4+ T cells from CIITAtgpIV−/− mice (A) and a human fetus (GA = 18 wk; B). This is compared with conventional CD4+ T cells from a WT mouse (A) and human cord blood (B). The data are mean values ± SEM of four animals in each group of mice, with one human fetus and four cord blood samples.

Mentions: Adaptive T cells are armed with a diverse repertoire of T cell receptors, whereas PLZF+ innate T cells, such as iNKT and MAIT cells, use a canonical Vα chain and a limited number of Vβ chains (Treiner and Lantz, 2006). As PLZF+ T–T CD4+ T cells are restricted by self-peptide–MHC class II complexes in mice, we hypothesized that the TCR Vβ repertoire of PLZF+ T cells in humans would be wider than that of iNKT (Vβ11) or MAIT (Vβ2 and Vβ13) cells (Treiner and Lantz, 2006). To confirm this, we analyzed their TCR Vβ chain usage. Based on their general diversity and frequency of individual Vβ chains, PLZF+ T–T CD4+ T cells and conventional CD4+ T cells isolated from the thymus or spleen of mice showed a similar TCR repertoire (Fig. 4 A). Furthermore, the diversity of TCR Vβ usage in human PLZF+ CD4+ T cells isolated from lymphoid tissue mimicked the Vβ usage of mouse T–T CD4+ T cells (Fig. 4 B). These data suggest that the development of PLZF+ CD4+ T cells in humans is similar to the development of T–T CD4+ T cells in mice.


Generation of PLZF+ CD4+ T cells via MHC class II-dependent thymocyte-thymocyte interaction is a physiological process in humans.

Lee YJ, Jeon YK, Kang BH, Chung DH, Park CG, Shin HY, Jung KC, Park SH - J. Exp. Med. (2009)

PLZF+ T–T CD4+ T cells in mice and humans have diverse TCR Vβ usage. The bar graph shows the Vβ chain distribution of PLZF+ and PLZF− CD4 SP thymocytes and splenic CD4+ T cells from CIITAtgpIV−/− mice (A) and a human fetus (GA = 18 wk; B). This is compared with conventional CD4+ T cells from a WT mouse (A) and human cord blood (B). The data are mean values ± SEM of four animals in each group of mice, with one human fetus and four cord blood samples.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2812550&req=5

fig4: PLZF+ T–T CD4+ T cells in mice and humans have diverse TCR Vβ usage. The bar graph shows the Vβ chain distribution of PLZF+ and PLZF− CD4 SP thymocytes and splenic CD4+ T cells from CIITAtgpIV−/− mice (A) and a human fetus (GA = 18 wk; B). This is compared with conventional CD4+ T cells from a WT mouse (A) and human cord blood (B). The data are mean values ± SEM of four animals in each group of mice, with one human fetus and four cord blood samples.
Mentions: Adaptive T cells are armed with a diverse repertoire of T cell receptors, whereas PLZF+ innate T cells, such as iNKT and MAIT cells, use a canonical Vα chain and a limited number of Vβ chains (Treiner and Lantz, 2006). As PLZF+ T–T CD4+ T cells are restricted by self-peptide–MHC class II complexes in mice, we hypothesized that the TCR Vβ repertoire of PLZF+ T cells in humans would be wider than that of iNKT (Vβ11) or MAIT (Vβ2 and Vβ13) cells (Treiner and Lantz, 2006). To confirm this, we analyzed their TCR Vβ chain usage. Based on their general diversity and frequency of individual Vβ chains, PLZF+ T–T CD4+ T cells and conventional CD4+ T cells isolated from the thymus or spleen of mice showed a similar TCR repertoire (Fig. 4 A). Furthermore, the diversity of TCR Vβ usage in human PLZF+ CD4+ T cells isolated from lymphoid tissue mimicked the Vβ usage of mouse T–T CD4+ T cells (Fig. 4 B). These data suggest that the development of PLZF+ CD4+ T cells in humans is similar to the development of T–T CD4+ T cells in mice.

Bottom Line: However, the developmental dissection of this T-T interaction in humans has not been possible because of the lack of known cellular molecules specific for T-T CD4+ T cells.Although these characteristics are quite similar to invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have a diverse T cell receptor repertoire and are restricted by MHC class II molecules.These findings define a novel human CD4+ T cell subset that develops via an MHC class II-dependent T-T interaction.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.

ABSTRACT
Human thymocytes, unlike mouse thymocytes, express major histocompatibility complex (MHC) class II molecules on their surface, especially during the fetal and perinatal stages. Based on this observation, we previously identified a novel developmental pathway for the generation of CD4+ T cells via interactions between MHC class II-expressing thymocytes (thymocyte-thymocyte [T-T] interactions) with a transgenic mouse system. However, the developmental dissection of this T-T interaction in humans has not been possible because of the lack of known cellular molecules specific for T-T CD4+ T cells. We show that promyelocytic leukemia zinc finger protein (PLZF) is a useful marker for the identification of T-T CD4+ T cells. With this analysis, we determined that a substantial number of fetal thymocytes and splenocytes express PLZF and acquire innate characteristics during their development in humans. Although these characteristics are quite similar to invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have a diverse T cell receptor repertoire and are restricted by MHC class II molecules. These findings define a novel human CD4+ T cell subset that develops via an MHC class II-dependent T-T interaction.

Show MeSH
Related in: MedlinePlus