Thymic modulation of IL-2 and IL-4 synthesis by peripheral T cells.
In this paper we provide several lines of evidence to support the hypothesis that the thymus can exert regulatory influences on the functional capabilities of mature recirculating T cells. Our studies demonstrate that while the IL-2-producing potential of T cells that repopulate the secondary lymphoid organs of lethally irradiated and stem cell-reconstituted mice is significantly reduced compared to that of T cells harvested from normal mice, the amount of IL-4 produced by the T cells of these experimental animals is equivalent to, or greater than, the amount produced by T cells from control animals. In addition, we determined that the amount of biologically active IL-2 and IL-4 secreted by T cells harvested from lethally irradiated animals who reconstitute their hematopoietic and immune systems under the influence of nonirradiated thymic epithelial grafts is essentially identical to the amount produced by T cells harvested from nonirradiated control animals. Collectively, these findings suggest that: (1) the alterations observed in the lymphokine-producing potential of T cells harvested from lethally irradiated and stem cell-reconstituted mice is not due to a direct effect of ionizing radiation on the T lymphocytes themselves, and (2) the exposure of the epithelial cells of the thymus to ionizing radiation during marrow-ablative regimens abrogates or modifies a component of thymic function which can influence the lymphokine-secreting potential of recirculating T cells. Further evidence for thymic involvement in the regulation of lymphokine production by peripheral T cells comes from our finding of a post-thymectomy time-dependent reduction in the capacity of T cells from animals to produce IL-2. Coincident with this reduction, T cells harvested from peripheral lymphoid organs of thymectomized animals demonstrated an augmentation in their IL-4-producing capabilities. The finding that treatment of thymectomized animals with the androgen steroid hormone dehydroepiandrosterone reestablished a normal IL-2-producing potential by their T cells makes it unlikely that the reduced capacity to produce IL-2 was secondary to a loss in fresh thymic emigrants.
Wiedmeier
S E
SE
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
Araneo
B A
BA
Huang
K
K
Daynes
R A
RA
D000818:Animals; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009924:Organ Culture Techniques; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D013934:Thymectomy; D013950:Thymus Gland / Q000502:physiology* / Q000528:radiation effects / Q000637:transplantation
D007376:Interleukin-2; D015847:Interleukin-4; D003687:Dehydroepiandrosterone