Using a transgenic mouse model we show that increased intrathymic expression of interleukin 4 (IL-4) significantly perturbs the development of thymocytes. Transgenic double-positive (CD4+CD8+) thymocytes, which are present in dramatically reduced numbers, exhibit increased T cell receptor (TCR) expression and increased mobilization of calcium mediated by these receptors. In contrast, transgenic single-positive (CD4+CD8- and CD4-CD8+) thymocytes and peripheral T cells exhibit decreased TCR-mediated calcium mobilization. The development of CD4-CD8+ thymocytes is significantly perturbed by IL-4 expressed in vivo; only peripheral CD4+ T cells are found in significant numbers in transgenic mice, while CD4-CD8+ thymocytes are present in increased numbers, apparently because of their failure to emigrate to the periphery. In contrast to these selective effects on T cell development, no significant differences in the numbers of B cells or mast cells, or in the plasma levels of IgE and IgG1 are observed between transgenic and control mice. These observations suggest that IL-4 in vivo exerts its major effects locally rather than systemically, even when its expression is constitutively increased.
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January 01 1991
Interleukin 4 expressed in situ selectively alters thymocyte development.
D B Lewis,
D B Lewis
Department of Pediatrics, University of Washington, Seattle 98195.
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C C Yu,
C C Yu
Department of Pediatrics, University of Washington, Seattle 98195.
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K A Forbush,
K A Forbush
Department of Pediatrics, University of Washington, Seattle 98195.
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J Carpenter,
J Carpenter
Department of Pediatrics, University of Washington, Seattle 98195.
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T A Sato,
T A Sato
Department of Pediatrics, University of Washington, Seattle 98195.
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A Grossman,
A Grossman
Department of Pediatrics, University of Washington, Seattle 98195.
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D H Liggitt,
D H Liggitt
Department of Pediatrics, University of Washington, Seattle 98195.
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R M Perlmutter
R M Perlmutter
Department of Pediatrics, University of Washington, Seattle 98195.
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D B Lewis
Department of Pediatrics, University of Washington, Seattle 98195.
C C Yu
Department of Pediatrics, University of Washington, Seattle 98195.
K A Forbush
Department of Pediatrics, University of Washington, Seattle 98195.
J Carpenter
Department of Pediatrics, University of Washington, Seattle 98195.
T A Sato
Department of Pediatrics, University of Washington, Seattle 98195.
A Grossman
Department of Pediatrics, University of Washington, Seattle 98195.
D H Liggitt
Department of Pediatrics, University of Washington, Seattle 98195.
R M Perlmutter
Department of Pediatrics, University of Washington, Seattle 98195.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1991) 173 (1): 89–100.
Citation
D B Lewis, C C Yu, K A Forbush, J Carpenter, T A Sato, A Grossman, D H Liggitt, R M Perlmutter; Interleukin 4 expressed in situ selectively alters thymocyte development.. J Exp Med 1 January 1991; 173 (1): 89–100. doi: https://doi.org/10.1084/jem.173.1.89
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