Monoclonal-nonspecific suppressor factor (
MNSF), a product of murine T cell hybridoma, suppresses antibody response to
lipopolysaccharide. In an attempt to clarify the functional mechanisms in vitro, we investigated the mode of action of
MNSF. This factor inhibited the antibody response by B cells (depleting T cells and Mø), thereby indicating that the lymphokine acts directly on B cells, without interaction between B and T cells or Mø.
MNSF activity was absorbed by
mitogen-stimulated T or B cells, but not by resting lymphocytes. Proliferative responses to T cell and B cell
mitogens were inhibited dose dependently by the addition of
MNSF. Kinetic studies showed that
MNSF suppressed the antibody response, in all culture periods, thereby indicating that
immunoglobulin secretion and proliferation were inhibited. The effect of
growth factor on
MNSF-mediated suppression was investigated to search for a possible suppression of
MNSF action.
Interleukin 2 (IL-2) remarkably inhibited
MNSF activity, and the effect of
IL-1 or
IL-4 was less.
IL-2 was most effective when added on the fourth day of culture.
MNSF also inhibits division in the
plasmacytoma line MOPC-31C or in
thymoma EL4, but not in L929 fibroblasts.
Tumor necrosis factor (TNF) inhibits cell division of various
tumor cells and suppresses the
pokeweed mitogen-induced antibody response, without cytotoxic action, as does
MNSF. While
MNSF and TNF have similar biochemical and physiochemical properties, the cross-reaction tests showed that both are antigenically discrete
lymphokines. Although
MNSF lacks TNF activity, the concomitant addition of both factors to L929 increases the cytotoxic action, a finding indicative of a synergistic effect.