CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo.
The innate and adaptive immune responses have evolved distinct strategies for controlling different viral pathogens. Encephalomyocarditis virus (EMCV) is a picornavirus that can cause paralysis, diabetes, and myocarditis within days of infection. The optimal innate immune response against EMCV in vivo requires CD1d. Interaction of antigen-presenting cell CD1d with distinct natural killer T-cell ("NKT") populations can induce rapid gamma interferon (IFN-gamma) production and NK-cell activation. The T-cell response of CD1d-deficient mice (lacking all NKT cells) against acute EMCV infection was further studied in vitro and in vivo. EMCV persisted at higher levels in CD1d-knockout (KO) splenocyte cultures infected in vitro. Furthermore, optimal resistance to repeat cycles of EMCV infection in vitro was also shown to depend on CD1d. However, this was not reflected in the relative levels of NK-cell activation but rather by the responses of both CD4(+) and CD8(+) T-cell populations. Repeated EMCV infection in vitro induced less IFN-gamma and alpha interferon (IFN-alpha) from CD1d-deficient splenocytes than with the wild type. Furthermore, the level of EMCV replication in wild-type splenocytes was markedly and specifically increased by addition of blocking anti-CD1d antibody. Depletion experiments demonstrated that dendritic cells contributed less than the combination of NK and NKT cells to anti-EMCV responses and that none of these cell types was the main source of IFN-alpha. Finally, EMCV infection in vivo produced higher levels of viremia in CD1d-KO mice than in wild-type animals, coupled with significantly less lymphocyte activation and IFN-alpha production. These results point to the existence of a previously unrecognized mechanism of rapid CD1d-dependent stimulation of the antiviral adaptive cellular immune response.
Ilyinskii
Petr O
PO
Cancer Biology Program, Hematology/Oncology Division, Beth Israel Deaconess Medical Center, NRB 1030L, 330 Brookline Avenue, Boston, MA 02215, USA.
Wang
Ruojie
R
Balk
Steven P
SP
Exley
Mark A
MA
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018188:Cardiovirus Infections / Q000235:genetics / Q000276:immunology*; D003920:Diabetes Mellitus / Q000276:immunology / Q000821:virology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D004680:Maus Elberfeld virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology / Q000821:virology; D010243:Paralysis / Q000276:immunology / Q000821:virology; D014766:Viremia / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; D016898:Interferon-alpha; D007371:Interferon-gamma