1380 Inducible Hybridoma Suppressor Cells

During the past several years, our laboratory has studied the mechanism of immune suppression in the 4-hydroxy-3-nitrophenyl acetyl (NP) 1 system. In this model system, both cell-mediated and humoral immunity (1-3) have been analyzed. The findings have permitted integration of the data into a single linear scheme of cellular interactions (3-5). Based on the results obtained in our and other laboratories that have investigated regulation by several types of suppressor T cells, we proposed that at least three distinct T cell subsets were involved in the phenomenon of immune suppression (3-5). These T cell subpopulations were termed Tsl, Ts~, and Ts~. The major criteria that are used to distinguish and identify the various cells in the suppressor cell pathway include: (a) the binding specificity of the relevant cells, i.e., do the cells bind antigen or idiotype; (b) the surface phenotype of the cells; (c) the genetic restrictions at either the H-2 or Igh gene complexes on the interactions of either the cells or their soluble factors (TsF); and (d) the kinetics of suppression, i.e., do the cells function in the induction or effector phase of the immune response? Tsx cells express the Ly-1+2 phenotype and possess NPb-related idiotypic receptors that bind antigen (1, 4). Tsx cells only function during the afferent or induction phase of the immune response (I), in contrast to the other forms of suppressor cells that can function during the effector or efferent phase of the immune response (4-6). Tsl cells and their factors (TsF1) function by stimulating a population of nonimmune T cells to become Tsz cells that are idiotyperather than antigen-specific (6, 7). It should be noted that these conclusions were mainly derived from experiments that used hybridoma-derived monoclonal TsF, to generate Tsz cells in the absence of antigen (7). Another important property of TsF~ is that it can induce Ts2 cells in any strain of mouse without genetic restrictions (7). Similar populations of Ts~-like inducer cells have been described in several other suppressor cell systems (8-13). Ts2 cells differ radically from Tsl in their properties and function. In the NP system, Ts2 cells are antiidiotypic and can be shown to bind idiotype-coated plates (6), although they do not bind the major NP b idiotypic determinants (14). Ts2 cells bear