TNF-ALPHA POTENTIATION OF THE LYMPHOKINE-ACTIVATED KILLER RESPONSE OFMURINE THYMUS-CELLS

The role of tumor necrosis factor (TNF-alpha) on in vitro generation o f lymphokine-activated killer (LAK) cells from murine thymocytes was i nvestigated and compared to that on generation of LAK from splenocytes . TNF-or increased the potential of interleukin-2 (IL-2) at suboptimal concentrations to generate LAK activity in thymocytes even more than in splenocytes. In parallel, augmented [H-3]thymidine uptake by thymoc ytes and splenocytes was seen. However, no net increase in viable cell number was observed. LAK effector cells from TNF-alpha plus IL-2 cult ures responded with an increased [H-3] thymidine uptake to restimulati on by IL-2 alone. These results suggest that TNF-alpha + IL-2 may be i nducing the expansion of a small subset of cells. NK1.1(+) cells are a very minor subset of thymocytes, nevertheless phenotype analysis show ed that in thymocytes, IL-2 + TNF-alpha generates NK1.1(+) CD8(-) LAK effectors in contrast to NK1.1(-) CD8(+) cells found with IL-2 alone. This result is consistent with the finding in the proliferation studie s. The fact that thymocytes are stimulated by the TNF-alpha + IL-2 com bination to proliferate as well as to develop a phenotypically distinc t effector supports the role of TNF-alpha in intra- and extrathymic re gulation.