Common γ-chain blocking peptide reduces in vitro immune activation markers in HTLV-1-associated myelopathy/tropical spastic paraparesis

Significance IL-2 and IL-15, members of the gamma chain family of cytokines, are prominently deregulated in human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and underlie many of the characteristic immune abnormalities such as spontaneous lymphocyte proliferation, increased STAT5 phosphorylation in the lymphocytes, and increased frequency and cytotoxicity of virus-specific CD8+ T lymphocytes (CTLs). In this in vitro study, we demonstrate that selective and simultaneous blockade of IL-2 and IL-15, with a γ-chain antagonistic peptide, reduces spontaneous lymphocyte proliferation (SP), STAT5 phosphorylation, and more important, the degranulation of CD8+ T cells and the frequency of HTLV-1-specific CTLs. Thus, selective cytokine blockade with antagonistic peptides might be a therapeutic approach in HAM/TSP and is potentially applicable to multiple other conditions in which cytokines are pathogenic.