CLASS-I-REACTIVE AND CLASS-II-REACTIVE TCR COEXPRESSED ON CD4(-CELL BOTH TRIGGER CD4() T)CD8-SHARED AND CD4-UNIQUE FUNCTIONS/

CD4(+) and CD8(+) T cells emerge from thymic selection expressing a TC R restricted by MHC class II (TCRII) and MHC class I (TCRI), and upon Ag stimulation develop respectively into Th and CTL effector cells, Th e influence of thymic differentiation and antigenic stimulation on the determination of T cell functions was studied, with CD4(+) T cells ex pressing a transgenic TCRI that reacts with the class I alloantigen H- 2K(b) in a CD8-independent fashion. Such T cells additionally express a TCR, probably TCRII, in which the transgenic TCR beta-chain is assoc iated with endogenously rearranged TCR alpha-chains. Upon in vitro sti mulation with H-2K(b)-expressing cells, both CD8(+) and CD4(+) transge nic TCR+ T cells developed into CTL capable of killing Ag-expressing t arget cells through a perforin-dependent mechanism, and secreted IL-2 and IFN-gamma. Fas ligand-dependent killing could also be induced in b oth CD8(+) and CD4(+) in vitro stimulated T cells, The capacity to sec rete IL-4 was restricted to the CD4(+) T cells, however, suggesting th at both CD8/CD4-shared and CD4-unique programs can be elicited by stim ulation of CD4 T cells through a TCRI. Acquisition of CTL function was also induced upon class Il alloantigen stimulation through the endoge nously rearranged TCRII, which represents a polyclonal set of TCRs, IL -2, IFN-gamma, and after restimulation, IL-4, were also produced, Thus : 1) events associated with intrathymic selection influence the gene p rogram activated in response to the same TCRI/APC interaction; and 2) CD4(+) T cells expressing a TCRI and a TCRII can activate the same gen e program after engagement of either one of these TCRs.