Cellular immune response in rnu/rnu rats. I. Lectin responsiveness and IL-2 production kinetics of natural cytotoxicity and spleen-cell surface marker expression.

Several functional parameters and surface markers were studied serially in rnu/rnu rats and compared to rnu/+ controls. Expressed as a percentage of labelled splenocytes, rnu/rnu animals had decreased W3/13 (P less than 0.01) and W3/25 (P less than 0.01) positive cells. Both W3/13 and W3/25 antigens peaked at Week 16 in rnu/rnu, but were still increasing after this date in rnu/+. In contrast, OX8 surface antigens were not significantly decreased at Week 19. However, if the low cell yield from rnu/rnu animals is taken into account, the expression of all studied surface markers was sharply decreased. Rnu/rnu splenocytes were almost totally unresponsive to either Con A or PHA stimulation, and were unable to produce significant amounts of IL-2 upon such stimulation. Moreover, the addition of exogenous semi-purified rat IL-2 could not restore lectin responsiveness. Natural cytotoxic activity of fresh splenocytes was studied against the NK-sensitive L 12.10 and MOLT-4 targets, normal cells after PHA stimulation and P 815 or Chang NK-resistant target cells. Rnu/rnu splenocytes exhibited a high level of natural cytotoxicity which peaked at Week 19 (four-fold higher than rnu/+ counterparts). Interestingly, NK-resistant and normal (LEW) PHA-blasts were also highly and efficiently lysed by rnu/rnu splenocytes, whereas rnu/+control exhibited only border line cytotoxicity. In contrast, rnu/rnu splenocytes cultured with IL-2 and allogeneic stimulation (both conditions being required to have enough rnu/rnu cultured cells for test) led to a dramatic drop in NK lysis, as compared to rnu/+ which retained a NK cytotoxicity level similar to that of fresh cells.