Analysis of an antigen-specific H-2-restricted cell-free products(s) made by "I-J-" Ly-2 cells (Ly-2 TsF) that suppresses Ly-2 cell-depleted spleen cell activity.

Immune Ly-1-,2+ splenic T cells release material(s) (Ly-2 TsF) into culture supernatants which (a) are antigen-specific and (b) do not contain gene products of the I-region of the MHC (major histocompatibility complex) (within the limits or our detection system) and which can lead to antigen-specific suppression of spleen cell cultures depleted of all Ly-2+ (Ly-2 and Ly-1,2) cells. The cells which make Ly-2 TsF possess no detectable I region- or Qa-1-encoded determinants. Nonetheless, the ability of the material(s) to suppress target cells is restricted by genes closely linked to the MHC. No demonstrable evidence for a role of the polymorphic portion of genes linked to the Ig locus for this suppressive interaction to occur could be found. It is suggested that this material(s) may be the final effector moiety of the suppressor circuit because (a) it does not require the presence of any Ly-2+ cells to work, and (b) in contrast to material(s) which induce suppression, there is no latent period; i.e. the Ly-2 TsF suppresses both the early and late phases of the immune response in primary Mishell-Dutton cultures. The MHC restriction that is imparted to the biologically active material is likely to be due to its "anti-MHC" activity. Since this is the first report in which the presence of I-J-controlled gene products was investigated on an antigen-specific, Ly-2 cell-produced suppressor factor that worked in the absence of Ly-2+ cells in the assay culture, the possibility that many, if not all, antigen-specific suppressor effector cells and molecules are "I-J-" must be considered.