Purified bovine WC1+ γδ T lymphocytes are activated by staphylococcal enterotoxins and toxic shock syndrome toxin-1 superantigens: proliferation response, TCR Vγ profile and cytokines expression

Abstract

In this study, the ability of purified bovine gammadelta T cells in vitro to be activated by superantigens (SAg) was investigated. Freshly isolated WC1(+) gammadelta T cells, in the presence of autologous glutaraldehyde-fixed or gamma-irradiated antigen presenting cells (APC) and IL-2, were incubated with staphylococcal enterotoxins A and B (SEA and SEB), and toxic shock syndrome toxin-1 (TSST-1). Both a proliferative response and the expression of particular T cell receptor genes of the gamma variable (TCR Vgamma) repertoire family were induced. Genes encoding TCR Vgamma1 and TCR Vgamma2 family, but not TCR Vgamma5 were detected. The cells also expressed cytokine transcripts, namely, those of IL-12, IFN-gamma and TNF-alpha, but not IL-2, IL-4, IL-6, IL-7 and IL-10. The activation and proliferation of freshly isolated gammadelta T cells by non-processed antigens required two signals, one originating from the APC and a second dependent on exogenous IL-2. Our results show that purified bovine WC1(+) gammadelta T cells could be driven to proliferate and to express a particular TCRVgamma profile in response to superantigen activation. The possible implication of cytokines expressed by bovine gammadelta T cells in immunopathogenesis is discussed.

Specific Recognition of Mycobacterial Protein and Peptide Antigens by γδ T Cell Subsets following Infection with VirulentMycobacterium bovis

“…Importantly, addition of exogenous IL-2 was required for significant gd T cell proliferation (data not shown). These results are in agreement with previous reports (61,62) and suggest that gd T cells likely require additional cytokine signals, such as IL-2 from ab T cells, to mount a full effector response.…”

Responses of Bovine WC1+γδ T Cells to Protein and Nonprotein Antigens ofMycobacterium bovis

“…Therefore, IL-2 alone can cause nonspecific activation of WC1 ϩ ␥␦ T cells but fails to initiate their proliferation. In agreement with previous reports for bovine ␥␦ T cells (11,17), IL-2 appeared to act as a costimulatory factor in antigendependent cell division. One of the immune mechanisms that has been suggested for the control of ␥␦ T-cell responses is the availability of IL-2 from CD4 ϩ T cells (51).…”

“…Proteins, in particular, may have a significant involvement in antigen-dependent IFN-␥ secretion by WC1 ϩ ␥␦ T cells, possibly enhancing their role in the development of Th1 biased antimycobacterial immunity through innate or adaptive production of IFN-␥ (22). Involvement of bovine WC1 ϩ ␥␦ T cells in innate production of IFN-␥ and IL-12 would be important functional roles, linking the innate and adaptive immune systems, as has been described for human ␥␦ T cells (7,17,29). …”

Interpretation of the Gamma Interferon Test for Diagnosis of Subclinical Paratuberculosis in Cattle

“…Many animals failed to respond to stimulation with ConA by producing IFN-␥, including animals in which PPD stimulation resulted in substantial IFN-␥ production. SEB is a superantigen that directly activates large fractions of bovine T cells by coupling to the V␤ (or V␥) T-cell receptor elements outside the antigen binding groove without a need for prior internalization and processing by antigen-presenting cells (15). By bromodeoxyuridine flow cytometry proliferation analysis (BD Biosciences), the major proliferating cell subpopulation following SEB stimulation of paraTB-infected or noninfected control animals are CD4 ϩ T cells (data not shown) while B cells and monocytes are not activated by SEB.…”