Fetal thymus graft enables recovery from age-related hearing loss and expansion of CD4-Positive T cells expressing IL-1 receptor type 2 and regulatory T Cells

Hiroshi Iwai, Muneo Inaba

Accumulating evidence has indicated the relationship between the systemic immune system and the central nervous system including the inner ear. We have shown that age-related developments of T-cell dysfunction, hearing loss, and degeneration of cochlear spiral ganglion (SG) neurons observed in 6-month-old mice were recovered in 12 months old mice which previously given fetal thymus transplants twice. We have also demonstrated that CD4(+) T cells expressing interleukin 1 receptor type 2 (IL-1R2) and naturally occurring regulatory T cells (nTregs), which expanded in aged 12-month-old mice, were reduced in the thymus-grafted mice of the same age. It is conceivable that the rejuvenation of systemic immune function by fetal thymus grafts contributes not only to the activation of cellular immunity but also to the decrease of IL-1R2(+) CD4(+) T cells or nTregs, which cells accelerate both age-related hearing loss (AHL) and neurodegeneration of the cochlear neurons. Further studies on the interactions among IL-1R2 expression on CD4(+) T cells, Tregs, and neuronal cells and also on the relationships between fetal thymus grafting and the rejuvenation of systemic immunity should be designed in order to advance towards therapeutic effects on neurosenescence, including AHL.