Journal of Experimental Medicine, Vol 173, 89-100, Copyright © 1991 by Rockefeller University Press

ARTICLES

Interleukin 4 expressed in situ selectively alters thymocyte development

DB Lewis, CC Yu, KA Forbush, J Carpenter, TA Sato, A Grossman, DH Liggitt and RM Perlmutter
Department of Pediatrics, University of Washington, Seattle 98195.

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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