ENDOGENOUS GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IS INVOLVED IN IL-1-INDUCED AND IL-7-INDUCED MURINE THYMOCYTE PROLIFERATION

We have reported previously that IL-1 induces murine thymocyte prolife ration in the absence of artificial comitogens, provided that the cell s are cultured at high densities. In the present study, we show that, in these conditions, TdR uptake in response to IL-1 is diminished sign ificantly by anti-granulocyte-macrophage colony-stimulating factor (GM -CSF) Abs. Indeed, a substantial production of this growth factor occu rs when thymocytes are cultured in the presence of IL-1. Maximal GM-CS F levels are attained within 3 days of culture, and mRNA expression is detected after a 48-h stimulation. Both CM-CSF production and IL-1-in duced thymocyte proliferation are decreased considerably by the deplet ion of I-A(+) Mac-1(+) accessory cells. Yet, addition of exogenous CM- CSF to accessory cell-depleted thymocytes does not restore the prolife rative response to IL-1 alone, suggesting the implication of another a ccessory 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 CM-CSF b y its specific Abs as by accessory cell removal (approximately 30%). F inally, 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 res ponse to IL-1 participates in IL-7-dependent, intrathymic expansion of the CD4(-)CD8(-)TCR(+) compartment.