title: Foot-and-mouth disease virus can induce a specific and rapid CD4+ T-cell-independent neutralizing and isotype class-switched antibody response in naïve cattle.
abstract: The role of T-lymphocyte subsets in recovery from foot-and-mouth disease virus (FMDV) infection in calves was investigated by administering subset-specific monoclonal antibodies. The depletion of circulating CD4(+) or WC1(+) gammadelta T cells was achieved for a period extending from before challenge to after resolution of viremia and peak clinical signs, whereas CD8(+) cell depletion was only partial. The depletion of CD4(+) cells was also confirmed by analysis of lymph node biopsy specimens 5 days postchallenge. Depletion with anti-WC1 and anti-CD8 antibodies had no effect on the kinetics of infection, clinical signs, and immune responses following FMDV infection. Three of the four CD4(+) T-cell-depleted calves failed to generate an antibody response to the nonstructural polyprotein 3ABC but generated a neutralizing antibody response similar to that in the controls, including rapid isotype switching to immunoglobulin G antibody. We conclude that antibody responses to sites on the surface of the virus capsid are T cell independent, whereas those directed against the nonstructural proteins are T cell dependent. CD4 depletion was found to substantially inhibit antibody responses to the G-H peptide loop VP1(135-156) on the viral capsid, indicating that responses to this particular site, which has a more mobile structure than other neutralizing sites on the virus capsid, are T cell dependent. The depletion of CD4(+) T cells had no adverse effect on the magnitude or duration of clinical signs or clearance of virus from the circulation. Overall, we conclude that CD4(+) T-cell-independent antibody responses play a major role in the resolution of foot-and-mouth disease in cattle.
authors.affiliation: Pirbright Laboratory, Institute for Animal Health, Ash Road, Woking, Surrey GU24 0NF, United Kingdom. nicholas.juleff@bbsrc.ac.uk
authors.forename: Nicholas
authors.initials: N
authors.lastname: Juleff
authors.forename: Miriam
authors.initials: M
authors.lastname: Windsor
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lefevre
authors.forename: Simon
authors.initials: S
authors.lastname: Gubbins
authors.forename: Pip
authors.initials: P
authors.lastname: Hamblin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Reid
authors.forename: Kerry
authors.initials: K
authors.lastname: McLaughlin
authors.forename: Peter C L
authors.initials: PC
authors.lastname: Beverley
authors.forename: Ivan W
authors.initials: IW
authors.lastname: Morrison
authors.forename: Bryan
authors.initials: B
authors.lastname: Charleston
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods; D009500:Neutralization Tests; D017361:Viral Nonstructural Proteins / Q000276:immunology; D015678:Viral Structural Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins