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 direct precursors, are readily converted to functional TCRhigh T cells by stimulation with immobilized TCR-specific mAb plus IL-2. Lineage decision invariably occurs toward CD4-8+, regardless of the timing of TCR stimulation after entry into the CD4+8+ compartment or the concentration of TCR-specific mAb used for stimulation. CD4-specific mAb synergizes with suboptimal TCR-specific mAb in inducing T cell maturation, but lineage decision remains exclusively CD4-8+. These results contrast with those obtained in mice, in which Abs to the TCR complex were shown to promote CD4+8- T cell maturation from CD4+8+ thymocytes. Surprisingly, when rat and mouse CD4+8+ thymocytes were stimulated with PMA/ionomycin under identical conditions, the opposite lineage commitment was observed, i.e., mouse thymocytes responded with the generation of CD4+8- and rat thymocytes with the generation of CD4-8+ cells. It thus seems that CD4+8+ thymocytes of the two species respond with opposite lineage decisions to strong activating signals such as given by TCR-specific mAb or PMA/ionomycin. A possible key to this difference lies in the availability of p56lck for coreceptor. supported signaling. We show that in contrast to mouse CD4+8+ thymocytes, which express both a complete and a truncated CD8 alpha-chain (CD8 alpha') unable to bind p56lck, rat thymocytes only express full-length CD8 alpha molecules. Mice, but not rats, therefore may use CD8 alpha' as a "dominant negative" coreceptor chain to attenuate the CD8 signal, thereby facilitating MHC class II recognition through the higher amount of p56lck delivered, and rats may use a different mechanism for MHC class distinction during positive selection.
Mitnacht
R
R
Institute for Virology and Immunobiology, University of Würzburg, Germany.
Bischof
A
A
Torres-Nagel
N
N
Hünig
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013045:Species Specificity; D013234:Stem Cells / Q000166:cytology; D017154:Stromal Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D007376:Interleukin-2; D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003208:Concanavalin A; D015847:Interleukin-4; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate