Non—MHC—restricted target—cell lysis by a CD4⁻CD⁻ TCRαβ T—cell line, as well as by TCR4gMδ T—cell lines, results from lymphokine—activated killing

A long—term CD4— CD8—TCR αβ human T—cell line, as well as similar CD4— CD8— TCR γδ T—cell lines for comparison, were generated from various tissues by negative selection using anti—CD4 and anti—CD8 monoclonal antibodies (MAbs) followed by positive selection with specific anti—TCR MAb and then repeated in vitro stimulation with interleukin—enriched media and lectin. These cell lines all demonstrated non—MHC—restricted cytolysis on a variety of human tumor cell lines. However, removal of lymphokines from the culture media for 24 hr abrogated most of the non—MHC—restricted target—cell lysis without affecting TCR αβ or TCR γδ cell viability or TCR function as determined by antibody—triggered redirected target—cell lysis. Subsequent re—exposure to lymphokines reconstituted non—MHC—restricted cytolysis by these cell lines. Thus, much of the non—specific, non—MHC—restricted cytolytic activity generated by CD4—CD8—TCRαβ or TCRγδ cells is secondary to lymphokine—activated killing (LAK) activity. These cells have potent LAK activity and may be prominent in LAK—cell populations. In addition, after lymphokine deprivation, both CD4—CD8—TCRαβ and TCRγδ cells showed residual activity against some tumor—cell targets, the nature of which remains to be defined.