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 ؉ ␥␦ 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 ؉

Type I and III IFNs Produced by Plasmacytoid Dendritic Cells in Response to a Member of theFlaviviridaeSuppress Cellular Immune Responses

“…As Fig. 1A shows, a significantly higher quantity of IFN was produced by pDCs (CD11c 2 , p = 0.0002) in response to ncp BVDV [XIKE A (29)] infection compared with cDCs (CD11c + ). These initial data confirmed bovine pDCs are the main source of the IFN generated in vitro by LLD cells in response to BVDV infection.…”

“…Previous work by our group showed pDCs are the major producers of type I IFN in response to FMDV infection (28). During this study, we investigated the levels of type I IFN present in serum samples from a cattle study of FMDV (O UKG) infection carried out by Juleff et al (29). These samples were reanalyzed before and after acid treatment to determine if the profile of type I and type III IFN was similar to the profile described in serum from BVDV-infected cattle.…”

“…All experiments were approved through the Institute's ethical review process and were in accordance with national guidelines on animal use. In a previous study, cattle were challenged with FMDV by subepidermolingual injection of 0.2 ml 10 5 50% tissue culture-infective doses into each of two sites with the cattle-adapted type O UKG/34/2001 strain of the virus (29). Serum samples from this previous study were used to assay for IFN.…”

Rapid and Transient Activation of γδ T Cells to IFN-γ Production, NK Cell-Like Killing, and Antigen Processing during Acute Virus Infection

“…In FMDV infection in particular, viral clearance is most likely mediated by many aspects of innate and adaptive immune responses. Minimally, there is a significant type I IFN response mediated by various dendritic cell populations (44,45), an early Ab response (41,46,47), and the gd T cell response reported in this study. We suggest that all of these responses can work concurrently, consistent with the observation that the high viral load is cleared so early and effectively.…”

Foot-and-Mouth Disease Virus Exhibits an Altered Tropism in the Presence of Specific Immunoglobulins, Enabling Productive Infection and Killing of Dendritic Cells

“…The host response to FMDV is dominated by the production of high titers of virus-neutralizing antibody, detectable from 3 days postinfection (11,29,54). The production of early antibody is T cell independent in both mice (9) and cattle (29).…”