Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces
inhibition of intrathymic T-cell development in hGM-CSF receptor transgenic
mice
Y Yasuda, I Nishijima, S Watanabe, K Arai, A Zlotnik and TA Moore
Department of Molecular and Developmental Biology, Institute of Medical
Science, University of Tokyo, Japan.
Thymocytes show differential cytokine responses, depending on the stage of
differentiation. Whether these responses are due to preferential cytokine
receptor expression or due to downstream signaling mechanisms is unknown.
In this study, we examined the relationship between receptor expression and
T-cell proliferation or differentiation using thymocytes from transgenic
mice constitutively expressing the human granulocyte-macrophage
colony-stimulating factor (hGM-CSF) receptor. Transgenic CD4- CD8-, CD4+
CD8-, and CD4- CD8+ cells proliferated when cultured with hGM-CSF in vitro,
whereas CD4+ CD8+ cells failed to proliferate. To examine the effect of
hGM-CSF receptor signaling on T- cell development, we used fetal thymic
organ cultures. The addition of exogenous hGM-CSF resulted in the failure
of CD4- CD8- cells to differentiate into CD4+ CD8+ cells. To more closely
identify this maturational inhibition, we reconstituted normal fetal lobes
with sorted pro-T-, pre-T-, or post-pre-T-precursor cells from transgenic
mice. The addition of hGM-CSF to these cultures led to a block in both
pro-T- and pre-T-cell differentiation, whereas the more mature post-pre- T
cells differentiated normally. We propose that hGM-CSF receptor signaling
during T-cell development results in a stage-specific inhibition of thymic
precursor maturation.
Volume 89,
Issue 4,
pp. 1349-1356,
02/15/1997
Copyright © 1997 by The American Society of Hematology
