Title: T cell functions under acidic conditions
It has been well known that solid cancer nests are acidified and immune cells infiltrate into such acidic cancer nests. However, immune cell functions under acidic conditions have not been focused. Our group has investigated the TCR signaling under acidic conditions with Jurkat T cells and human peripheral primary T cells. In Jurkat T cells, the phosphorylation of CD3 and ZAP-70 was induced by the CD3 stimulation at pH 6.3 as well as pH 7.6. Calcium ions were mobilized by the CD3 stimulation at pH 7.6 and the mobilization was strengthened by the co-stimulation with CD28. In contrast to alkaline pH, no calcium ion mobilization was induced by the CD3 stimulation or co-stimulation of CD3 and CD28 at pH 6.3. Neither the stimulation of CD3 nor the co-stimulation of CD3 and CD28 induced the expression of interleukins at pH 6.3. The same results were obtained in human peripheral primary T cells. These results suggest that the downstream pathway of the TCR-signaling does not work in T cells infiltrated into acidic cancer nests. This may be a reason for attenuation of immune cell functions in cancer nests.