gamma delta(+) T-lymphocyte cytotoxicity against envelope-expressing target cells is unique to the alymphocytic state of bovine leukemia virus infection in the natural host

Bovine leukemia virus (BLV) is a complex B-lymphotrophic retrovirus of catt le and the causative agent of enzootic bovine leukosis, Serum antibody in i nfected animals does not correlate with protection from disease, yet only s ome animals develop severe disease. While a cytotoxic T-lymphocyte response may be responsible for directing BLV pathogenesis, this possibility has be en left largely unexplored, in part since the lack of readily established c ytotoxic target cells in cattle has hampered such studies. Using long-term naturally infected alymphocytic (AL) cattle, we have established the existe nce of cytotoxic T-lymphocyte response against BLV envelope proteins (Env; gp51/gp30), In vitro-expanded peripheral blood mononuclear (PBM) cell effec tor populations consisted mainly of gamma delta(+) (>40%), CD4(+) (>35%), a nd CD8(+) (>10%) T lymphocytes. Specific lysis of autologous fibroblasts in fected with recombinant vaccinia virus (rVV) delivering the BLV env gene ra nged from 30 to 65%. Depletion studies indicated that gamma delta(+) and no t CD8(+) T cells were responsible for the cytotoxicity against autologous r VVenv-expressing fibroblasts. Additionally, cultured effector cells lysed r VVenv-expressing autologous fibroblasts and rVVenv-expressing xenogeneic ta rgets similarly, suggesting a lack of genetic restricted killing. Restimula tion of effector populations increased the proportion of gamma delta(+) T c ells and concomitantly Env-specific cytolysis, Interestingly, culture of ce lls from BLV negative or persistently lymphocytic cattle failed to elicit s uch cytotoxic responses or increase in gamma delta(+) T-cell numbers. These results imply that cytotoxic gamma delta(+) T lymphocytes from only AL cat tle recognize BLV Env without a requirement for classical major histocompat ibility complex interactions. It is known that gamma delta(+) T lymphocytes are diverse and numerous in cattle, and here we show that they may serve a surveillance role during natural BLV infection.