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.
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.
Juleff
Nicholas
N
Pirbright Laboratory, Institute for Animal Health, Ash Road, Woking, Surrey GU24 0NF, United Kingdom. nicholas.juleff@bbsrc.ac.uk
Windsor
Miriam
M
Lefevre
Eric A
EA
Gubbins
Simon
S
Hamblin
Pip
P
Reid
Elizabeth
E
McLaughlin
Kerry
K
Beverley
Peter C L
PC
Morrison
Ivan W
IW
Charleston
Bryan
B
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
D000914:Antibodies, Viral; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins