Induction of T cell proliferation and cytotoxicity by lymphokines.

Induction of cytotoxic T lymphocyte (CTL) responses i n v i t r o requires a series of d i s c r e t e a c t i v a t i o n s i g n a l s . CTL-precursors (CTL-p) express receptors for the T c e l l growth factor i n t e r l e u k i n 2 (IL-2) a f t e r an i n i t i a l antigen or mitogen stimulus. The presence of IL-2 i s necessary for sustained T c e l l growth, i . e . , IL-2 receptor-bearing T c e l l s expand c l o n a l l y by consuming IL-2 (1~3). Requirement f or other lymphokines to convert CTL-p into funct i o n a l CTL-effector c e l l s has been described previously (4-8). In mixed lymphocyte c u l t u r e s , a l l necessary helper signals are provided by c e l l s w i t h i n the c u l t u r e s . Culture conditions with lim i t e d helper potent i a l were established i n order to study the required helper mediators. When l i m i t e d numbers ( 1 0 5 ) of unfractionated thymocytes were cultured i n the presence of metabolically i n a c t i v e stimulator c e l l s , even very high concent r a t i o n s of p u r i f i e d mouse or recombinant human IL-2 were unable to induce either p r o l i f e r a t i v e or cytotoxic responses ( 8 ) .