Selective lymphocyte depletion during the early stage of the immune response to foot-and-mouth disease virus infection in swine.
Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious vesicular disease of cloven-hoofed animals. In the present study we use FMDV serotype C infection of swine to determine, by analytical techniques, the direct ex vivo visualization of virus-infected immune cells during the first 17 days of infection. We report, for the first time, that FMDV C-S8c1 can infect T and B cells at short periods of time postinoculation, corresponding with the peak of the viremia. There is a significant lymphopenia that involves CD3(+) CD4(-) CD8(+/-), CD3(+) CD4(-) CD8(+)Tc, and CD3(+) CD4(+) CD8(+) memory Th but not CD3(+) CD4(+) CD8(-) naïve Th lymphocytes. In addition, a profound depletion of the vast majority of peripheral T cells in lymph nodes and spleen is observed. This selective depletion of T cells is not due mainly to in situ death via apoptosis as visualized by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. Thus, early infection of T cells by FMDV may be the main cause of the observed T-cell depletion. Importantly, this lack of T cells is reflected in a reduced response to mitogen activation, which in many cases is totally eliminated. These data suggest a mechanism by which the virus causes a transient immunosuppression, subvert the immune systems, and spreads. These results have important implications for our understanding of early events in the development of a robust immune response against FMDV.
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Spain.
Fayna
F
Díaz-San Segundo
Francisco J
FJ
Salguero
Ana
A
de Avila
M Mar Fernández
MM
de Marco
Miguel A
MA
Sánchez-Martín
Noemí
N
Sevilla
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D005260:Female; D005536:Foot-and-Mouth Disease / Q000276:immunology* / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D007108:Immune Tolerance; D020287:In Situ Nick-End Labeling; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008231:Lymphopenia; D013154:Spleen / Q000473:pathology; D013552:Swine; D013553:Swine Diseases / Q000276:immunology* / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology / Q000821:virology*