THE ACTIONS OF POLYNUCLEOTIDES ON EFFECTOR STAGE CLONED MURINE T-HELPER CELLS DIFFER IN EACH SUBSET AND DEPEND ON ANTIGEN CONCENTRATION

Polynucleotides enhance T-helper (Th) cell-mediated humoral immune res ponses in naive resting Th cells, B cells, and antigen-presenting cell s (APC) from unprimed mouse spleen. If polynucleotides augment Th cell functions independent of the activation stage of Th cells, then polyn ucleotides may cause hyperimmune responses. In this study we examined the effects of polynucleotides on effector-stage murine Th cell clones in vitro. The A.E7 clone (primed with pigeon cytochrome C, origin: B1 0.A mice) and CDC35 clone (primed with rabbit gamma-globulin, origin: DBA/2 mice) were used as representative type 1 (Th1) and type 2 (Th2) Th cells, respectively. Th clones were stimulated with antigen (Ag) in polynucleotide-supplemented or control cultures in the presence of sy ngeneic spleen cells (either CD4(-) or irradiated). The number of anti body (Ab)-secreting cells was counted to measure T-dependent Ab produc tion. Production of interferon-gamma (IFN gamma) for the Th1 clone and interleukin-5 (IL-5) for the Th2 clone were measured. Without Ag stim ulation, cytokine production and the number of Ab-secreting cells form ed were very low and not altered by polynucleotides. With suboptimal A g challenges provided by Ag-primed spleen cells, polynucleotides enhan ced IFN gamma production by the Th1 clone, while they suppressed Th1 c lone-mediated Ab production and IL-5 production by the Th2 clone. Poly nucleotides did not alter Th2 clone-mediated Ab production. These acti ons of polynucleotides appeared to be dose-dependent. With optimal Ag challenges, polynucleotides did not affect our measures of Th cell act ivation. Polynucleotide action in vitro on effector-stage Th cell clon es differed in each Th cell subset and depended on Ag concentration.