Type I interferon (IFN alpha) acts directly on human memory CD4+ T cells altering their response to antigen.
Despite its use widely as a therapeutic agent, and proposed use as vaccine adjuvant, the effect of IFNalpha on T cell function is poorly understood. As a pleiotropic innate cytokine produced rapidly in response to pathogens, it is well placed to impinge on specific immune responses. The aim of this study was to examine the impact of IFNalpha on the function of human memory CD4(+) T cells using the recall Ags purified protein derivative, tetanus toxoid, and hemagglutinin. IFNalpha administered either in vivo or added exogenously in vitro tended to enhance proliferative responses of purified protein derivative-specific T cells in marked contrast to the other cognate populations whose responses were often diminished. Purifying the memory CD4(+)CD45RO(+) T cells confirmed IFNalpha acted directly on these cells and not via an intermediate. The T cells could be divided into two broad categories depending on how IFNalpha effected their responses to cognate Ag: 1) enhanced proliferation and a striking increase in IFNgamma-production compared with smaller increases in IL-10 (increased ratio of IFNgamma:IL-10), and 2) neutral or diminished proliferation coupled with a smaller increase in IFNgamma relative to the increase in IL-10 (reduced IFNgamma:IL-10 ratio). IFNalpha has a role in modifying memory T cell responses when they are exposed to cognate Ag and may be important in vaccination strategies designed to augment particular Th memory responses.
Gallagher
Kathleen M E
KM
Department of Medical Biochemistry and Immunology, Cardiff University, Cardiff, United Kingdom.
Lauder
Sarah
S
Rees
Ian W
IW
Gallimore
Awen M
AM
Godkin
Andrew J
AJ
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000494:pharmacology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000502:physiology* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D013745:Tetanus Toxoid / Q000494:pharmacology; D014373:Tuberculin / Q000494:pharmacology
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016898:Interferon-alpha; D013745:Tetanus Toxoid; D014373:Tuberculin