GENERATION OF IN-VITRO NATURAL CYTOTOXICITY OF HORSE LYMPHOCYTES AGAINST SARCOID-DERIVED TUMOR-CELLS NOT EXPRESSING MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS

Objective-To analyze in vitro lymphocyte-mediated immune responses of horses with sarcoids against allogeneic sarcoid cells containing endog enous retrovirus but not expressing major histocompatibility complex a ntigens. Design-Lymphocyte-mediated immune reactions were assessed by means of proliferative responses in mixed lymphocyte tumor cell cultur e (MLTC) assay and lymphocyte-mediated cytotoxicity against various eq uine target cells. Animals-12 horses with sarcoid tumors and 15 contro l horses. Procedure-Blood lymphocytes were cocultured in MLTC with all ogeneic sarcoid cells (Mc-1, BayMc-1), equine testis cells, or normal equine dermal fibroblasts. Lymphocytes were assayed for proliferative responses by [H-3]thymidine uptake and for cytotoxicity against the sa me targets by Cr-51 release assay. The lymphocyte populations were ana lyzed for some common surface markers. Results-Lymphocytes from horses with sarcoids exerted an anamnestic proliferative response in MLTC ag ainst Mc-1 cells, but this procedure never generated cytotoxic lymphoc ytes. However, lymphocytes from ail horses cultured in medium with 10% allogeneic serum only had selective, natural cytotoxicity against Mc- 1 that was generated without DNA synthesis. Approximately 80% of the l ymphocytes disappeared during culture, however the remaining populatio n of small, viable lymphocytes indicated a decrease of CD4(+) and CD8( +) T lymphocytes, but numbers of T cells with receptors for Helix poma tia A hemagglutinin were unaffected. Few lymphocytes had Fc-receptors for IgG, were complement-reactive positive cells, or were B cells expr essing surface immunoglobulin, Conclusions-Results may indicate a natu ral defense system, which preferentially recognizes and lyses tumor ce lls that are deficient in surface expression of major histocompatibili ty complex antigens, without intervention of conventional T-cell recep tors or antibodies.