title: Tentative T cells: memory cells are quick to respond, but slow to divide.
abstract: T cell memory is a cornerstone of protective immunity, and is the key element in successful vaccination. Upon encountering the relevant pathogen, memory T cells are thought to initiate cell division much more rapidly than their naïve counterparts, and this is thought to confer a significant biological advantage upon an immune host. Here, we use traceable TCR-transgenic T cells to evaluate this proposed characteristic in CD4+ and CD8+ memory T cells. We find that, even in the presence of abundant antigen that was sufficient to induce in vivo IFNgamma production by memory T cells, both memory and naïve T cells show an extended, and indistinguishable, delay in the onset of proliferation. Although memory cells can detect, and respond to, virus infection within a few hours, their proliferation did not begin until approximately 3 days after infection, and occurred simultaneously in all anatomical compartments. Thereafter, cell division was extraordinarily rapid for both naïve and memory cells, with the latter showing a somewhat accelerated accumulation. We propose that, by permitting memory T cells to rapidly exert their effector functions while delaying the onset of their proliferation, evolution has provided a safeguard that balances the risk of infection against the consequences of severe T cell-mediated immunopathology.
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Whitmire
authors.forename: Boreth
authors.initials: B
authors.lastname: Eam
authors.forename: J Lindsay
authors.initials: JL
authors.lastname: Whitton
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007108:Immune Tolerance; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D011500:Protein Synthesis Inhibitors; D011948:Receptors, Antigen, T-Cell; D020126:Brefeldin A; D007371:Interferon-gamma