Distinct thresholds for CD8 T cell activation lead to functional heterogeneity: CD8 T cell priming can occur independently of cell division.
To examine the bases for CD8 T cell functional heterogeneity, we analyzed responses to partial vs full agonist Ag. An extended period of interaction with APCs was required to set the threshold required for cell division in response to partial as compared with full agonist Ag. Acquisition of cytolytic function was restricted to the divided T cell population. In contrast, the threshold for commitment to produce IFN-gamma and express some activation markers appeared lower and independent of cell division. Indeed, we characterized a T cell population stimulated in response to the partial agonist that was committed to produce IFN-gamma, but failed to divide or secrete IL-2. Importantly, this activated nondivided population behaved as "primed" rather than "anergized," indicating 1) that priming of CD8 T cells may be induced by suboptimal stimulation independent of cell division and 2) that encounter with Ag does not always induce a complete differentiation program in naive CD8 T cells, as previously reported.
Auphan-Anezin
Nathalie
N
Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université de la Méditerranée, Campus de Luminy, Marseille, France. auphan@ciml.univ-mrs.fr
Verdeil
Grégory
G
Schmitt-Verhulst
Anne-Marie
AM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018740:Genetic Heterogeneity; D006183:H-2 Antigens / Q000235:genetics / Q000502:physiology; D007114:Immunization; D007117:Immunization, Secondary; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell