Endogenous granulocyte-macrophage colony-stimulating factor is involved in IL-1- and IL-7-induced murine thymocyte proliferation.
We have reported previously that IL-1 induces murine thymocyte proliferation in the absence of artificial comitogens, provided that the cells are cultured at high densities. In the present study, we show that, in these conditions, TdR uptake in response to IL-1 is diminished significantly by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) Abs. Indeed, a substantial production of this growth factor occurs when thymocytes are cultured in the presence of IL-1. Maximal GM-CSF levels are attained within 3 days of culture, and mRNA expression is detected after a 48-h stimulation. Both GM-CSF production and IL-1-induced thymocyte proliferation are decreased considerably by the depletion of I-A+ Mac-1+ accessory cells. Yet, addition of exogenous GM-CSF to accessory cell-depleted thymocytes does not restore the proliferative response to IL-1 alone, suggesting the implication of another accessory cell-derived mediator. Our data design IL-7 as the endogenous factor required in our culture system because: 1) GM-CSF can reverse the decrease in the proliferation after accessory cell depletion when IL-7 is provided together with IL-1, and 2) the proliferative response to IL-1 plus IL-7 is diminished as much by neutralization of GM-CSF by its specific Abs as by accessory cell removal (approximately 30%). Finally, the cells responding to IL-1 + IL-7 were identified as mature CD4-CD8-TCR+ thymocytes by the use of bromodeoxyuridine (BrdUrd), suggesting that the GM-CSF produced by thymic accessory cells in response to IL-1 participates in IL-7-dependent, intrathymic expansion of the CD4-CD8-TCR+ compartment.
Herbelin
A
A
INSERM U 25, Necker Hospital, Paris, France.
Machavoine
F
F
Vicari
A
A
Schneider
E
E
Papiernik
M
M
Ziltener
H
H
Penit
C
C
Dy
M
M
D000818:Animals; D000938:Antigen-Presenting Cells; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*
D007375:Interleukin-1; D015851:Interleukin-7; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor