Brief antigenic stimulation generates effector CD8 T cells with low cytotoxic activity and high IL-2 production.
It is currently believed that a brief antigenic stimulation is sufficient to induce CD8 T cells to complete their differentiation program, become effector T cells, and subsequently generate memory. Because this concept was derived from studies in which only a single effector function was analyzed (either IFN-gamma production or target cell lysis), we wondered whether monitoring for multiple effector functions might reveal novel characteristics of effector CD8 T cells elicited by brief or prolonged Ag exposure. Using an in vitro system to generate effector T cells and an in vivo adoptive transfer model to track donor CD8 T cells, we found that the differentiation programs acquired by CD8 T cells after brief or prolonged antigenic stimulation were different. Although the frequencies of IFN-gamma and TNF-alpha producers were comparable for both effector CD8 T cell populations, there were major differences in cytotoxic potential and IL-2 production. Whereas prolonged (>24 h) Ag exposure stimulated effector CD8 T cells with high cytotoxic activity and low IL-2 production, brief (<24 h) stimulation generated effector CD8 T cells with low cytotoxic activity and high IL-2 production. The latter effector T cells rapidly converted into central memory-like CD8 T cells, exhibited long-term survival in adoptively transferred hosts, and gave robust recall responses upon Ag challenge. These data suggest that not all functions of effector CD8 T cells are equally inherited after brief or prolonged antigenic stimulation.
Usharauli
David
D
T Cell Tolerance and Memory Section (Ghost Lab), Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. dusharauli@niaid.nih.gov
Kamala
Tirumalai
T
D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D010641:Phenotype
D000941:Antigens; D018398:Homeodomain Proteins; D007376:Interleukin-2; C064658:RAG-1 protein