Enhanced secretion of interferon-gamma by bovine gammadelta T cells induced by coculture with Mycobacterium bovis-infected dendritic cells: evidence for reciprocal activating signals.

Evidence suggests that gammadelta T cells form part of the innate immune response to Mycobacterium bovis infection. Dendritic cells (DCs) are capable of secreting high levels of interleukin-12 (IL-12) following infection with mycobacteria and can induce interferon-gamma (IFN-gamma) secretion by natural killer and gammadelta T cells We investigated the innate interactions occurring between WC1(+)gammadelta T cells and M. bovis-infected DCs. Following coculture with M. bovis-infected DCs, secretion of IFN-gamma and expression of CD25 and major histocompatibility complex class II on WC1(+)gammadelta T cells were significantly enhanced. Reciprocal enhancement of IL-12 secretion by the DCs was also observed and this interaction was found to be contact dependent. We hypothesize that there is an early, transient signal between the WC1(+)gammadelta T cells and the DCs, which promotes the synthesis of biologically active IL-12, and which is dependent upon cell-cell contact. Reciprocal signals including IL-12 are then delivered to WC1(+)gammadelta cells, which leads to the enhanced secretion of IFN-gamma, and the up-regulation of activation markers and antigen presentation molecules by the WC1(+)gammadelta T cells. These interactions are likely to form a critical part of the T helper type 1-conditioning response of DCs to M. bovis.

Workshop cluster 1+ gammadelta T-cell receptor T cells from calves express high levels of interferon-gamma in response to stimulation with interleukin-12 and -18.

Gammadelta T-cell receptor(+) T lymphocytes are an important element of the innate immune system. Early production of interferon (IFN)-gamma by gammadelta T cells may have a role in linking innate and adaptive immune responses and contribute to T helper-1 bias. We investigated the role of cytokines in the activation and induction of IFN-gamma secretion by bovine workshop cluster 1(+) (WC1(+)) gammadelta T cells. The effects of culture with interleukin (IL)-12, IL-18, IL-15 and IL-2 were investigated; these cytokines are known to influence murine and human gammadelta T cells. We report that bovine WC1(+)gammadelta T cells are synergistically stimulated by IL-12 and IL-18 to secrete large quantities of IFN-gamma. Neonatal calves were shown to have significantly higher numbers of circulating WC1(+)gammadelta T cells than adult animals. In addition, the response of peripheral blood WC1(+)gammadelta T cells was significantly higher in neonatal calves compared with adult animals. However, in adult animals the response of lymph node WC1(+)gammadelta T cells to IL-12/IL-18 was more pronounced than that of peripheral blood WC1(+)gammadelta T cells. We hypothesize that the induction of IFN-gamma secretion from WC1(+)gammadelta T cells by IL-12 and IL-18 is likely to be an important element of the innate response to pathogens such as Mycobacterium bovis. The high numbers of WC1(+)gammadelta T cells in neonatal calves, and their inherent ability to respond to inflammatory cytokines, could be a key factor in the enhanced responses seen in calves to BCG vaccination.