TNF-alpha potentiation of the lymphokine-activated killer response of murine thymus cells
Ujházy, P.; Maccubbin, D.; Eppolito, C.; Mihich, E.; Ehrke, M.J.
Lymphokine and Cytokine Research 13(2): 99-106
1994
ISSN/ISBN: 1056-5477 PMID: 8061121 Document Number: 422659
The role of tumor necrosis factor (TNF-alpha) on in vitro generation of lymphokine-activated killer (LAK) cells from murine thymocytes was investigated and compared to that on generation of LAK from splenocytes. TNF-alpha 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 (3H)thymidine uptake by thymocytes and splenocytes was seen. However, no net increase in viable cell number was observed. LAK effector cells from TNF-alpha plus IL-2 cultures responded with an increased (3H)thymidine uptake to restimulation by IL-2 alone. These results suggest that TNF-alpha + IL-2 may be inducing the expansion of a small subset of cells. NK1.1+ cells are a very minor subset of thymocytes, nevertheless phenotype analysis showed 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 studies. The fact that thymocytes are stimulated by the TNF-alpha + IL-2 combination to proliferate as well as to develop a phenotypically distinct effector supports the role of TNF-alpha in intra- and extrathymic regulation.