title: Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes.
abstract: The lineage relationship between short-lived effector T cells and long-lived memory cells is not fully understood. We have described T-GFP mice previously, in which naive and early activated T cells express GFP uniformly, whereas cells that have differentiated into effector cytotoxic T cells selectively lose GFP expression. Here we studied antigen-specific CD8 T cell differentiation using T-GFP mice crossed to the TCR transgenic (Tg) mice P14 (specific for the lymphocytic choriomeningitis virus glycoprotein peptide, gp33-41). After activation with antigenic peptide, P14XT-GFP CD8(+) T cells cultured in high-dose IL-2 developed into cells with effector phenotype and function: they were blastoid, lost GFP expression, expressed high levels of activation and effector markers, and were capable of immediate cytotoxic function. In contrast, cells cultured in IL-15 or low-dose IL-2 never developed into full-fledged effector cells. Rather, they resembled memory cells: they were smaller, were GFP(+), did not express effector markers, and were incapable of immediate cytotoxicity. However, they mediated rapid-recall responses in vitro. After adoptive transfer, they survived in vivo for at least 10 weeks and mounted a secondary immune response after antigen rechallenge that was as potent as endogenously generated memory cells. In addition to providing a simple means to generate memory cells in virtually unlimited numbers, our results suggest that effector differentiation is not a prerequisite for memory cell generation.
authors.affiliation: The Center for Blood Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA. swamy@cbr.med.harvard.edu
authors.forename: N
authors.initials: N
authors.lastname: Manjunath
authors.forename: P
authors.initials: P
authors.lastname: Shankar
authors.forename: J
authors.initials: J
authors.lastname: Wan
authors.forename: W
authors.initials: W
authors.lastname: Weninger
authors.forename: M A
authors.initials: MA
authors.lastname: Crowley
authors.forename: K
authors.initials: K
authors.lastname: Hieshima
authors.forename: T A
authors.initials: TA
authors.lastname: Springer
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: J
authors.initials: J
authors.lastname: Lieberman
authors.forename: U H
authors.initials: UH
authors.lastname: von Andrian
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D006023:Glycoproteins / Q000276:immunology; D049452:Green Fluorescent Proteins; D007156:Immunologic Memory; D066298:In Vitro Techniques; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008164:Luminescent Proteins / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D019409:Interleukin-15; D007376:Interleukin-2; D008164:Luminescent Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; D049452:Green Fluorescent Proteins