Bovine gamma/delta T-cell proliferation is associated with self-derived molecules constitutively expressed in vivo on mononuclear phagocytes.

Bovine gamma/delta T cells have been shown previously to proliferate when cocultured with gamma-irradiated bovine monocytes in the 'autologous mixed leucocyte reaction' (AMLR). It was suggested that the response may be to culture-derived or culture-induced antigenic epitopes. Data presented here indicate that the gamma/delta T-cell stimulatory activity is attributable to a self-derived cell-surface molecule of mononuclear phagocytes that is constitutively expressed in vivo. The ability to induce an AMLR did not require in vitro culture or stress associated with in vitro isolation of cells or increased temperature since it could be induced by monocytes fixed by paraformaldehyde during blood collection from normal animals. Furthermore, stimulation by monocytes did not depend upon secreted molecules since fixed monocytes that had been incubated overnight at 37 degrees to allow secretion of preformed molecules, or subjected to hypotonic shock in H2O for 10 min before addition to the cultures, induced an AMLR as did plasma membranes prepared from ex vivo monocytes. In contrast, enzymatic treatment of monocytes to digest surface molecules followed by fixation destroyed their ability to stimulate an AMLR. The ability of monocytes to stimulate proliferation of gamma/delta T cells was distinguishable from their ability to stimulate alpha/beta T cells, since the former was destroyed by glutaraldehyde fixation whereas stimulation of alpha/beta T cells by major histocompatibility complex (MHC)-presented antigenic epitopes is not. Moreover, induction of proliferation of bovine gamma/delta T cells was not MHC-restricted. Finally, bovine alveolar macrophages, sheep monocytes and transformed bovine monocytes stimulated proliferation of bovine gamma/delta T cells whereas none of the following did so: human monocytes, murine macrophages, bovine myeloid cells other than mononuclear phagocytes, other nucleated cells found in bovine blood including activated MHC class II-bearing B cells, and a variety of species of bacteria. Thus, the stimulatory epitope is unique to and conserved among mononuclear phagocytes of ruminants. Demonstration of stimulation of bovine gamma/delta T cells by self-derived molecules is consistent with reports for murine gamma/delta T cells.