The Actions of Polynucleotides on Effector Stage Cloned Murine T-Helper Cells Differ in Each Subset and Depend on Antigen Concentration

Abstract

Polynucleotides enhance T-helper (Th) cell-mediated humoral immune responses in naive resting Th cells, B cells, and antigen-presenting cells (APC) from unprimed mouse spleen. If polynucleotides augment Th cell functions independent of the activation stage of Th cells, then polynucleotides 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: B10.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 syngeneic spleen cells (either CD4- or irradiated). The number of antibody (Ab)-secreting cells was counted to measure T-dependent Ab production. Production of interferon-gamma (IFNgamma) for the Th1 clone and interleukin-5 (IL-5) for the Th2 clone were measured. Without Ag stimulation, cytokine production and the number of Ab-secreting cells formed were very low and not altered by polynucleotides. With suboptimal Ag challenges provided by Ag-primed spleen cells, polynucleotides enhanced IFNgamma production by the Th1 clone, while they suppressed Th1 clone-mediated Ab production and IL-5 production by the Th2 clone. Polynucleotides did not alter Th2 clone-mediated Ab production. These actions of polynucleotides appeared to be dose-dependent. With optimal Ag challenges, polynucleotides did not affect our measures of Th cell activation. Polynucleotide action in vitro on effector-stage Th cell clones differed in each Th cell subset and depended on Ag concentration.