title: Effector functions of memory CTLs can be affected by signals received during reactivation.
abstract: Memory cytotoxic T lymphocytes (CTLs) are able to provide protections to the host against repeated insults from intracellular pathogens. However, it has not been completely understood how the effector functions of memory CTLs are induced upon antigen challenge, which is directly related to the efficacy of their protection. Third signal cytokines, such as IL-12 and type I interferon, have been suggested to be involved in the protective function of memory CTLs, but direct evidence is warranted. In this report, we found that memory CTLs need to be reactivated to exert effector functions. Infusion of a large population of quiescent memory CTLs did not lead to cancer control in tumor-bearing mice, whereas infusion of a reactivated memory CTL population did. This reactivation of memory CTLs requires cytokines such as IL-12 in addition to antigen but was less dependent upon costimulation and IL-2 compared to naive CTLs. Memory CTLs responded more quickly and with greater strength than their naive counterparts upon stimulation, which is associated with higher upregulation of important transcription factors such as T-bet and phosphorylated STAT4. In addition, memory CTLs underwent less expansion than naive CTLs upon pathogen challenge. In conclusion, effector functions of established memory CTLs may be affected by certain cytokines such as IL-12 and type I IFN. Thus, a pathogen's ability to induce cytokines could contribute to the efficacy of protection of an established memory CTL population.
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD, 20742, USA.|College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, 210095, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Elliot
authors.initials: E
authors.lastname: Mattson
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Anjuli
authors.initials: A
authors.lastname: Bhadurihauck
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Karla
authors.initials: K
authors.lastname: Garcia
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD, 20742, USA. xiao0028@umd.edu.
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016922:Cellular Senescence; D007156:Immunologic Memory; D007157:Immunologic Surveillance; D007370:Interferon Type I / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D007370:Interferon Type I; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D050797:STAT4 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12
keywords: Activation; CTLs; Interleukin-12; Memory; Type I interferon; Vaccination