Role of a Distinct Population of Bovine γδ T Cells in the Immune Response to Viral Agents

Abstract

A distinct population of bovine gamma delta T cells was isolated from peripheral blood mononuclear cells of foot-and-mouth disease (FMD)-vaccinated cattle; these lymphocytes were shown to exert a natural killer-like activity against cells infected by different viruses. The antiviral activity was dependent upon cognate recognition of target cells and could operate by both cytostatic and cytotoxic mechanisms. Among these, secretion of a serine esterase was shown after binding to target cells. This population of bovine gamma delta T cells is recognized by murine monoclonal antibodies 1E7, 5D4, and 6F9, raised in our laboratory. To define an in vivo antiviral role, four heifers were infected with a strain of bovid herpesvirus 1 by the intranasal/intravaginal routes and contact exposure. The prevalence of 1E7+/5D4+ cells among peripheral blood lymphocytes increased dramatically in the first days after infection; the same held true for in-contact cattle, albeit with a different time kinetics. In another experiment, colonization of mucosae was demonstrated by immunoperoxidase staining on tongue and palate sections of healthy cattle. The infiltration of gamma delta T cells altogether in the palate mucosa was much more accentuated in foot-and-mouth disease-vaccinated, as compared to nonvaccinated, control calves.

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

“…They showed that spontaneous killing was exhibited when parasite-stimulated WC1 + cells were presented with a xenogeneic NK-sensitive target cell line. More relevant to the current study, Amadori et al (12) showed activation of bovine gd T lymphocytes following vaccination of calves against FMDV. In those studies, gd T cells were capable of lysing target cells in a manner similar to NK cells, indicating that either a spontaneous killing capability develops in this population of T cells or their reactivity could be driven by specific viral Ag recognition.…”

“…This may suggest activation of gd T cells following infection with O1 Manisa FMDV. A clearly activated status of bovine gd T cells was shown by Amadori et al (12) in their experiments with bovine herpes virus, in which a sharp increase of gd T cells was detected on the first day postinfection. We show increase in the relative percentage of gd TCR-expressing cells only on day 3 postinfection with FMDV relative to preinfection.…”

“…In cattle, studies have shown a dramatic increase in gd T cells in the peripheral blood of cattle within the first days of infection with bovine herpesvirus type I. Furthermore, cattle vaccinated against FMDV were reported to have increased numbers of gd T cells that adopted a NK-like phenotype and, like human cells, were capable of lysing virus-infected target cells (12). Similarly, in bovine viral diarrhea virus infection, gd T cells increased 100-fold (13).…”

In Vitro Responsiveness of γδ T Cells fromMycobacterium bovis-Infected Cattle to Mycobacterial Antigens: Predominant Involvement of WC1+Cells

“…A range of functions, including proliferation and natural killer and cytotoxic activity, have been documented for bovine ␥␦ T cells in response to mitogens and parasite, bacterial, and viral antigens (1,14,15,16,19), and it is likely that such functions could be involved in the defense against M. bovis. Furthermore, it has previously been demonstrated that the WC1 ϩ cells are among the first T cells to show changes in circulating numbers and antigen responsiveness following experimental M. bovis infection of cattle (53).…”

γδ+T-Lymphocyte Cytotoxicity against Envelope-Expressing Target Cells Is Unique to the Alymphocytic State of Bovine Leukemia Virus Infection in the Natural Host

“…Most relevant to the present study is herpes simplex virus infection, where ␥␦ ϩ T cells have been shown to directly recognize the gI protein (51) and also correlate with protection (30,51,52). In addition, ␥␦ ϩ T cells are notably activated in cytomegalovirus (14), influenza virus (26), and Sendai virus (37) infections and, importantly, in several bovine viral infections such as those caused by bovine respiratory syncytial virus (50), bovine herpesvirus 1 (47), and foot-andmouth disease virus (3). Activated ␥␦ ϩ T cells are also evident during simian and human immunodeficiency virus (SIV and HIV) infections, although their presence does not necessarily correlate with protection (63; reviewed in reference 41), and activated ␥␦ ϩ T cells in SIV and HIV infections also react to certain cells lines (17,57; reviewed in references 8 and 28).…”