Interleukin 2 (IL2) has demonstrated a potent ability to augment NK activity and the generation of killers against NK insensitive targets. This IL2-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. These in vitro results are consistent with the hypothesis that IL2 is the major inducer of LAK activity and that other recombinant cytokines do not appear to regulate either the progenitor or effector stages of lAK activity. In addition to mediating NK activity, LGL have been shown to produce a variety of lymphokines (IL1, IFN, CSF, BCGF). A project investigating gene expression and regulation in highly purified human LGL and T cells is being conducted. Within 1 hr after IL2 treatment of freshly isolated human LGL, IFN-gamma mRNA can be detected with IFn-gamma protein in the culture medium within 4-6 hours of treatment. These results indicate that with certain stimuli LGL may be the predominant source of IFn-gamma from peripheral blood lymphocytes. The methylation state of the T cell receptor beta-chain gene (T-beta) DNA of T cells, LGL, B cells and monocytes is being studied to determine if it can be used as a marker for different leukocyte populations. In addition to IL2, the interaction of specific surface proteins, as potential regulatory elements are being examined. Specific monoclonal antibodies have been used to examine this question. The results have demonstrated that anti-CD2 monoclonal antibodies have significant regulatory abilities on functions of CD3-LGL. In addition, preliminary results have demonstrated that combinations of antibodies with specificity for selected epitopes of CD2 can result in significant synergy as determined by NK activity and IFN gamma production.
