Interleukin 4 expressed in situ selectively alters thymocyte development.
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.
Lewis
D B
DB
Department of Pediatrics, University of Washington, Seattle 98195.
Yu
C C
CC
Forbush
K A
KA
Carpenter
J
J
Sato
T A
TA
Grossman
A
A
Liggitt
D H
DH
Perlmutter
R M
RM
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D007132:Immunoglobulin Isotypes / Q000097:blood; D015847:Interleukin-4 / Q000502:physiology*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D007132:Immunoglobulin Isotypes; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D015847:Interleukin-4