IL-4, IL-10, IL-13, and TGF-beta from an altered peptide ligand-specific Th2 cell clone down-regulate adoptive transfer of experimental antoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is induced in the SJL/J mou se by adoptive transfer of activated proteolipid protein peptide (PLP) 139- 151-specific Th1 cells. T cells responding to altered peptide ligands (APL) of PLP, previously shown to induce Th2 differentiation and regulate diseas e in PLP-immunized mice, do not transfer EAE, However, the exact mechanism of disease regulation by APL-specific T cells has not been elucidated, In t his report, we show that 1F1, a Th2 done specific for an APL of PLP139-151d z can prevent adoptive transfer of EAE when cocultured with PLP-encephalito genic spleen cells (PLP-spleen), Cytokines from activated 1F1 cells were de tected by hybridization of mRNA to oligonucleotide arrays (DNA chip) and by ELISA, The Th2 cytokines found to be present at the highest protein and mR NA levels were evaluated for their role in suppression of adoptive transfer of EAE from PLP-activated spleen cell cultures. Abs to individual cytokine s in 1F1 PLP-spleen cocultures suggested that IL-4, IL-13, and TGF-beta pla yed a significant role in suppressing EAE. Abs to the combination of IL-4, IL-10, IL-13, and TGF-beta completely neutralized the protective effect of 1F1, Addition of Th2 cytokines to PLP-spleen cultures showed that IL-13 and TGF-beta were each individually effective and low levels of IL-4 synergize d with IL-13 to inhibit disease transfer. IL-5, IL-9, and IL-10 had little or no effect whereas GM-CSI; slightly enhanced EAE, Our results demonstrate that Th2 cytokines derived from APL-specific Th2 cells can effectively dow n-regulate the encephalitogenic potential of PLP-spleen cells if present du ring their reactivation in culture.