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 w hen cocultured with gamma-irradiated bovine monocytes in the 'autologo us mixed leucocyte reaction' (AMLR). It was suggested that the respons e may be to culture-derived or culture-induced antigenic epitopes. Dat a presented here indicate that the gamma/delta T-cell stimulatory acti vity is attributable to a self-derived cell-surface molecule of mononu clear phagocytes that is constitutively expressed in vivo. The ability to induce an AMLR did not require in vitro culture or stress associat ed with in vitro isolation of cells or increased temperature since it could be induced by monocytes fixed by paraformaldehyde during blood c ollection from normal animals. Furthermore, stimulation by monocytes d id not depend upon secreted molecules since fixed monocytes that had b een incubated overnight at 37 degrees to allow secretion of preformed molecules, or subjected to hypotonic shock in H2O for 10 min before ad dition to the cultures, induced an AMLR as did plasma membranes prepar ed from ex vivo monocytes. In contrast, enzymatic treatment of monocyt es to digest surface molecules followed by fixation destroyed their ab ility to stimulate an AMLR. The ability of monocytes to stimulate prol iferation of gamma/delta T cells was distinguishable from their abilit y to stimulate alpha/beta T cells, since the former was destroyed by g lutaraldehyde fixation whereas stimulation of alpha/beta T cells by ma jor histocompatibility complex (MHC)-presented antigenic epitopes is n ot. Moreover, induction of proliferation of bovine gamma/delta T cells was not MHC-restricted. Finally, bovine alveolar macrophages, sheep m onocytes 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 mononu clear phagocytes, other nucleated cells found in bovine blood includin g activated MHC class II-bearing B cells, and a variety of species of bacteria. Thus, the stimulatory epitope is unique to and conserved amo ng mononuclear phagocytes of ruminants. Demonstration of stimulation o f bovine gamma delta T cells by self-derived molecules is consistent w ith reports for murine gamma/delta T cells.