T11TS immunotherapy potentiates the repressed calcineurin‐NFAT signalling pathway of T cells in Cryptococcus neoformans infected rats: a cue towards T‐cell activation for antifungal immunity.

Aims: To examine the modulation of the interacting partners of the calcineurin (CaN)‐NFAT pathway in T cells during Cryptococcus neoformans fungal infection and post‐T11TS immunotherapy. Methods and Results: Wistar rats were infected with C. neoformans and followed by immunotherapy with immune‐potentiator T11TS. T cells were analysed by flow cytometry, immunoblotting and nuclear translocation study. The signalling proteins LCK, FYN, LAT, PLCγ1 and CaN in T cells were regulated by C. neoformans infection resulting in reduced nuclear translocation of NFAT and IL‐2 expression. Following T11TS immunotherapy, the expressions of the above‐mentioned proteins were boosted and thus resulting in the clearance of C. neoformans from lung and spleen. Conclusions: The precise mechanism of suppression of the T‐cell function by C. neoformans is still unknown. Previously, we have shown that T11TS positively regulates the function of T cells to abrogate glioma and other immunosuppressive conditions. T11TS immunotherapy increased the expression of the above signalling partners of the CaN‐NFAT pathway in T cells and improved nuclear retention of NFAT. As a result, an increased IL‐2 expression leads to activation and proliferation of T cells. Significance and Impact of the Study: Our results demonstrate the role of T11TS in restoring the CaN‐NFAT signalling pathway in T cells. It identifies T11TS as an immunotherapeutic agent with potential clinical outcomes to counteract C. neoformans infection. [ABSTRACT FROM AUTHOR]