Selective Expansion of Double-Negative iNKT Cells Inhibits the Development of Atopic Dermatitis in VαE14 TCR Transgenic NC/Nga Mice by Increasing Memory-Type CD8+ T and Regulatory CD4+ T Cells

Spontaneous development of atopic dermatitis (AD) in NC/Nga (NC) mice has been attributed to a deficiency in invariant NK T (iNKT) cells. To elucidate the precise role of iNKT cells in AD development of NC mice, we employed two distinct murine models of iNKT cell over-representation: V beta 8 TCR congenic and V alpha 14 TCR transgenic NC mice. We found that V alpha 14 TCR transgenic (V alpha 14(Tg)) but not V beta 8 TCR congenic (V beta 8(Cg)) NC mice exhibited reduced AD development, which was attributed to both quantitative and qualitative changes in iNKT cells such as a biased expansion of the double-negative iNKT subset. Adoptive transfer experiments confirmed that iNKT cells from V alpha 14(Tg) mice but not from V beta 8(Cg) mice were responsible for protecting NC mice from AD development. Double-negative iNKT cells from V alpha 14(Tg) NC mice showed a T helper type-1-dominant cytokine profile, which may account for the expansion of CD4(+) regulatory T cells and memory-type CD8(+) T cells. Furthermore, the adoptive transfer of CD8(+)T cells from V alpha 14(Tg) NC mice into AD-susceptible wild-type NC mice suppressed AD in recipient NC mice. Taken together, our results have identified double-negative iNKT cells as promising cellular targets to prevent AD pathogenesis.