Human natural killer (NK) cells and K cells mediating antibody-dependent cellular cytotoxicity have been shown to be large granular lymphocytes (LGL). Interferon caused augmentation of NK and K cell activities of LGL and only LGL demonstrated either spontaneous or interferon-activated NK activity. Natural, recombinant and hybrid recombinant alpha, beta, and gamma interferon molecules have been shown to augment NK activity but vary widely in their potency relative to antiviral activity. Recombinant interferon-gamma, both glycosylated and non-glycosylated were very weak boosters of NK activity. IL-2 (T cell growth factor), in addition to IFN, has demonstrated a potent ability to augment NK activity. This IL-2-mediated augmentation appears to parallel production of IFN-Gamma by LGL, but abrogation of antiviral activity with anti-IFN-Gamma serum did not abolish NK boosting. IL-2 activation of LGL resulted in the generation of killers against targets that were NK insensitive to fresh or IFN activated LGL. Results have indicated that LAK cells are generated from NK cells and that the majority of LAK activity against non-immunogenic tumors is derived from LGL. Studies were also performed to examine the therapeutic efficacy of antibody-dependent cellular cytotoxicity (ADCC) with murine and human monoclonal antibodies. ADCC with murine anti-melanoma monoclonal antibodies could be substantially augmented with recombinant interferon and IL-2. Cultures and clones of highly purified LGL, grown in the presence of IL-2 have demonstrated morphology and cytotoxic patterns similar to fresh LGL. In addition to NK activity, cultured and clones of LGL have been shown to produce a variety of lymphokines (IL-1, IFN, CSF, BCGF).
