Limits...
Distinct roles for signals relayed through the common cytokine receptor gamma chain and interleukin 7 receptor alpha chain in natural T cell development.

Boesteanu A, Silva AD, Nakajima H, Leonard WJ, Peschon JJ, Joyce S - J. Exp. Med. (1997)

Bottom Line: However, the absolute number of NK1(+) T cells in the thymus of IL-7Ralpha-deficient mice is reduced to approximately 10%, compared to natural T cell number in the wild-type thymus.Additional data revealed that NK1(+) T cell ontogeny is not impaired in IL-2- or IL-4-deficient mice, suggesting that neither IL-2, IL-4, nor IL-7 are required for their development.From these data, we conclude that commitment and/or differentiation to the NK1(+) natural T cell lineage requires signal transduction through the gammac, and once committed, their expansion requires signals relayed through the IL-7Ralpha.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.

ABSTRACT
The commitment, differentiation, and expansion of mainstream alpha/beta T cells during ontogeny depend on the highly controlled interplay of signals relayed by cytokines through their receptors on progenitor cells. The role of cytokines in the development of natural killer (NK)1(+) natural T cells is less clearly understood. In an approach to define the role of cytokines in the commitment, differentiation, and expansion of NK1(+) T cells, their development was studied in common cytokine receptor gamma chain (gammac) and interleukin (IL)-7 receptor alpha (IL-7Ralpha)-deficient mice. These mutations block mainstream alpha/beta T cell ontogeny at an early prethymocyte stage. Natural T cells do not develop in gammac-deficient mice; they are absent in the thymus and peripheral lymphoid organs such as the liver and the spleen. In contrast, NK1(+) T cells develop in IL-7Ralpha-deficient mice in the thymus, and they are present in the liver and in the spleen. However, the absolute number of NK1(+) T cells in the thymus of IL-7Ralpha-deficient mice is reduced to approximately 10%, compared to natural T cell number in the wild-type thymus. Additional data revealed that NK1(+) T cell ontogeny is not impaired in IL-2- or IL-4-deficient mice, suggesting that neither IL-2, IL-4, nor IL-7 are required for their development. From these data, we conclude that commitment and/or differentiation to the NK1(+) natural T cell lineage requires signal transduction through the gammac, and once committed, their expansion requires signals relayed through the IL-7Ralpha.

Show MeSH
Common cytokine  receptor γc-deficient mice do not  develop thymic NTα/β cells.  Dot plots displaying CD44+  NKR-P1+ and CD44+TCR-α/β+ T cells among HSAlow  CD8low thymocytes of B6.γc0/Y  (seventh generation backcross to  C57BL/6) and B6.IL-2Rγc+/Y  littermates. HSAlowCD8low thymocyte population was electronically gated and CD44highNKR-P1+ T cells were analyzed with a  FACScan® flow cytometer.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2198975&req=5

Figure 1: Common cytokine receptor γc-deficient mice do not develop thymic NTα/β cells. Dot plots displaying CD44+ NKR-P1+ and CD44+TCR-α/β+ T cells among HSAlow CD8low thymocytes of B6.γc0/Y (seventh generation backcross to C57BL/6) and B6.IL-2Rγc+/Y littermates. HSAlowCD8low thymocyte population was electronically gated and CD44highNKR-P1+ T cells were analyzed with a FACScan® flow cytometer.

Mentions: The loss of γc expression as found in X-linked severe combined immunodeficiency patients or in mice results in impaired development of mainstream α/β T cells (15, 17). To determine whether γc deficiency affects NT cell ontogeny, we examined their development in the thymus of γc0/Y mice backcrossed to C57BL/6 for 4–8 generations. γc0/Y mice, >6 wk old, do not develop HSAlowCD8low CD44highNKR-P1+ thymocytes, whereas they are detected in the γc+/Y wild-type littermates (Fig. 1). Thus, akin to mainstream T cells, signaling through γc is important for NT cell ontogeny.


Distinct roles for signals relayed through the common cytokine receptor gamma chain and interleukin 7 receptor alpha chain in natural T cell development.

Boesteanu A, Silva AD, Nakajima H, Leonard WJ, Peschon JJ, Joyce S - J. Exp. Med. (1997)

Common cytokine  receptor γc-deficient mice do not  develop thymic NTα/β cells.  Dot plots displaying CD44+  NKR-P1+ and CD44+TCR-α/β+ T cells among HSAlow  CD8low thymocytes of B6.γc0/Y  (seventh generation backcross to  C57BL/6) and B6.IL-2Rγc+/Y  littermates. HSAlowCD8low thymocyte population was electronically gated and CD44highNKR-P1+ T cells were analyzed with a  FACScan® flow cytometer.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198975&req=5

Figure 1: Common cytokine receptor γc-deficient mice do not develop thymic NTα/β cells. Dot plots displaying CD44+ NKR-P1+ and CD44+TCR-α/β+ T cells among HSAlow CD8low thymocytes of B6.γc0/Y (seventh generation backcross to C57BL/6) and B6.IL-2Rγc+/Y littermates. HSAlowCD8low thymocyte population was electronically gated and CD44highNKR-P1+ T cells were analyzed with a FACScan® flow cytometer.
Mentions: The loss of γc expression as found in X-linked severe combined immunodeficiency patients or in mice results in impaired development of mainstream α/β T cells (15, 17). To determine whether γc deficiency affects NT cell ontogeny, we examined their development in the thymus of γc0/Y mice backcrossed to C57BL/6 for 4–8 generations. γc0/Y mice, >6 wk old, do not develop HSAlowCD8low CD44highNKR-P1+ thymocytes, whereas they are detected in the γc+/Y wild-type littermates (Fig. 1). Thus, akin to mainstream T cells, signaling through γc is important for NT cell ontogeny.

Bottom Line: However, the absolute number of NK1(+) T cells in the thymus of IL-7Ralpha-deficient mice is reduced to approximately 10%, compared to natural T cell number in the wild-type thymus.Additional data revealed that NK1(+) T cell ontogeny is not impaired in IL-2- or IL-4-deficient mice, suggesting that neither IL-2, IL-4, nor IL-7 are required for their development.From these data, we conclude that commitment and/or differentiation to the NK1(+) natural T cell lineage requires signal transduction through the gammac, and once committed, their expansion requires signals relayed through the IL-7Ralpha.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.

ABSTRACT
The commitment, differentiation, and expansion of mainstream alpha/beta T cells during ontogeny depend on the highly controlled interplay of signals relayed by cytokines through their receptors on progenitor cells. The role of cytokines in the development of natural killer (NK)1(+) natural T cells is less clearly understood. In an approach to define the role of cytokines in the commitment, differentiation, and expansion of NK1(+) T cells, their development was studied in common cytokine receptor gamma chain (gammac) and interleukin (IL)-7 receptor alpha (IL-7Ralpha)-deficient mice. These mutations block mainstream alpha/beta T cell ontogeny at an early prethymocyte stage. Natural T cells do not develop in gammac-deficient mice; they are absent in the thymus and peripheral lymphoid organs such as the liver and the spleen. In contrast, NK1(+) T cells develop in IL-7Ralpha-deficient mice in the thymus, and they are present in the liver and in the spleen. However, the absolute number of NK1(+) T cells in the thymus of IL-7Ralpha-deficient mice is reduced to approximately 10%, compared to natural T cell number in the wild-type thymus. Additional data revealed that NK1(+) T cell ontogeny is not impaired in IL-2- or IL-4-deficient mice, suggesting that neither IL-2, IL-4, nor IL-7 are required for their development. From these data, we conclude that commitment and/or differentiation to the NK1(+) natural T cell lineage requires signal transduction through the gammac, and once committed, their expansion requires signals relayed through the IL-7Ralpha.

Show MeSH