OPPOSITE CD4 CD8 LINEAGE DECISIONS OF CD4(+)8(+) MOUSE AND RAT THYMOCYTES TO EQUIVALENT TRIGGERING SIGNALS - CORRELATION WITH THYMIC EXPRESSION OF A TRUNCATED CD8-ALPHA CHAIN IN MICE BUT NOT RATS/

Unselected CD4(+)8(+) rat thymocytes, generated in vitro from their di rect precursors, are readily converted to functional TCRhigh T cells b y stimulation with immobilized TCR-specific mAb plus IL-2. Lineage dec ision invariably occurs toward CD4(-)8(+), regardless of the timing of TCR stimulation after entry into the CD4(+)8(+) compartment or the co ncentration of TCR-specific mAb used for stimulation. CD4-specific mAb synergizes with suboptimal TCR-specific mAb in inducing T cell matura tion, but lineage decision remains exclusively CD4(-)8(+). These resul ts contrast with those obtained in mice, in which Abs to the TCR compl ex were shown to promote CD4(+)8(-) T cell maturation from CD4(+)8(+) thymocytes, Surprisingly, when rat and mouse CD4(+)8(+) thymocytes wer e stimulated with PMA/ionomycin under identical conditions, the opposi te lineage commitment was observed, i.e., mouse thymocytes responded w ith the generation of CD4(+)8(-) and rat thymocytes with the generatio n of CD4(-)8(+) cells. It thus seems that CD4(+)8(+) thymocytes of the two species respond with opposite lineage decisions to strong activat ing signals such as given by TCR-specific mAb or PMA/ionomycin. A poss ible key to this difference lies in the availability of p56(lck) for c oreceptor-supported signaling, We show that in contrast to mouse CD4()8(+) thymocytes, which express both a complete and a truncated CD8 al pha-chain (CD8 alpha') unable to bind p56(lck), rat thymocytes only ex press full-length CD8 alpha molecules. Mice, but not rats, therefore m ay use CD8 alpha' as a ''dominant negative'' coreceptor chain to atten uate the CD8 signal, thereby facilitating MHC class II recognition thr ough the higher amount of p56(lck) delivered, and rats may use a diffe rent mechanism for MHC class distinction during positive selection.