Formation of IgE-binding factors by rat T lmphocytes. III. Mechanisms of selective formation of IgE-suppressive factors by treatment with complete Freund's adjuvant

Splenic lymphocytes of rats treated by repeated injections of complete Freund's adjuvants (CFA) spontaneously released soluble factors that had affinity for IgE and selectively suppressed the IgE response (IgE-suppressive factors). The factors lacked affinity for lentil lectin. The serum of CFA-treated rats and culture filtrates of their spleen cells induced normal mesenteric lymph node (MLN) cells to form IgE-suppressive factors. Analysis of the cellular mechanisms for the induction of IgE-suppressive factors in CFA-treated animals revealed that their macrophages formed 'inducers' of IgE-binding factors; their splenic lymphocytes released another soluble factor(s) that could modulate the nature of the IgE-binding factors. Culture filtrates of splenic, adherent cells from the CFA-treated animals induced normal MLN cells to form IgE-binding factors, but the factors failed to suppress the IgE response. However, normal MLN cells formed IgE-suppressive factors when they were incubated with a mixture of culture filtrates of adherent and nonadherent cells from CFA-treated rats or with culture filtrates of nonadherent cells and IgE. Approximately one-half of IgE-binding factors induced by IgE or 'inducer' alone had affinity for lentil lectin. If the IgE-binding factors were induced in the presence of culture filtrates of splenic lymphocytes from CFA-treated animals, however, the majority of the factors lacked affinity for the lectin. The same culture filtrate prevented the IgE-induced increase in Fc(ε)R(+) cells in both B cell and T cell populations. The results indicate that splenic lymphocytes release lymphokines that prevent the glycosylation of the precursor molecules of both Fc(ε)R and IgE-binding factors, thereby preventing the expression of Fc(ε)R and increasing the ratio of the IgE-suppressive factors to the total IgE-binding factors. The source of the glycosylation-inhibiting factors appears to be a subset of T cells lacking W 3/25 markers, whereas the source of the IgE-suppressive factors is W 3/25(+) T cells. Macrophage-derived 'inducers' of IgE-binding factors had affinity for Poly U Sepharose and could be recovered from the beads by elution with 1 M NaCl. The results indicate that collaboration between 'inducers' derived from adherent cells and 'glycosylation-inhibiting factors' from W 3/25(-)T cells results in the formation of IgE-suppressive factors by W 3/25(+) T cells.