Activation of murine CD8+ lymphocytes: two distinct signals regulate c-myc and interleukin 2 receptor RNA expression

Resting cytotoxic T lymphocyte precursors (CTL-P; CD8+) constitutively express T cell receptors (TcR) on their cell surfaces. CTL-P are preactivated if binding of the corresponding antigen (mitogens, allogeneic major histocompatibility complex (MHC) determinants, viral proteins or haptens in conjunction with self MHC structures) to the TcR takes place. Using a myc-specific probe I show that within 12 h first antigen binding leads to optimal c-myc RNA expression which seems to be the first sign that resting CTL-P are preactivated. Thereafter, c-myc RNA expression was remarkably reduced only at day 5. Antigen alone, however, is not sufficient for interleukin 2 receptor (IL2R) RNA expression. A monocyte-derived, soluble mediator termed IL2R-inducing factor (RIF) acts in conjunction with antigen to induced the expression of IL2R RNA and functional IL2R on the cell surface. RIF is a 44-kDa heat-labile protein produced by accessory cells and its function is restricted to CD8+ lymphocytes. IL2R RNA is first expressed 12 h after onset of culture, maximally expressed on day 3 and it decreases thereafter. Cells kept in long-term culture without mitogen but in the presence of IL2 do not express high amounts of IL2R RNA. Expression of IL2R RNA can be very efficiently reinduced, however, by mitogenic stimulation. In contrast to primary cultures, IL2R RNA expression peaks earlier and is independent of RIF. The results obtained here show that (a) for CD8+ lymphocytes of primary cultures two distinct activation signals (mitogen and RIF) are necessary for c-myc and IL2R RNA expression and (b) for CD8+ lymphocytes of secondary cultures the mitogenic signal alone is sufficient for re-expression of IL2R RNA.