Regulatory T_R3-56 Cells in the Complex Panorama of Immune Activation and Regulation

Round 1

Reviewer 1 Report

I really enjoyed the reading of this review paper. The review is very fluid, clear and synthetically addressing one of the main issues on immunoregulation.Indeed, the review addresses a very interesting topic, succeeding in offering the reader a wide and broad overview of the interaction between immune activation and immune regulation. In this sense, the examination of molecules and cells involved in immune regulation appears complete and exhaustively treated. At the same time, the argument on the TR3-56 population also appears very interesting. TR3-56 cells have been characterized by the same Authors in some articles, suggesting a regulatory role in autoimmune (DOI: 10.1038/s42255-020-0173-1) and oncohematological diseases ( DOI: 10.1111/ejh.13822; DOI: 10.1111/ejh.13931). Taken together, according to the previous comments,  this excellent review article appears worthy of publication as it stands in the current form, in my frank opinion.

Author Response

The Authors sincerely thank the Reviewer for appreciating the topic of the Review.

Reviewer 2 Report

This manuscript clearly analyzed the complexity and the sophisticated interplay of diversified T cells during immune activation and immune regulation. The extensive description for the delicate balance between correct and effective immune defense and preventing excessive pathogenic harms. Authors report a succinct overview of complicated balance between activation and inhibition of innate and adaptive immune responses. They pointed out the critical investigation of T_R3-56 could inspire to deepen the exploration on the immune flexible system. The original and pioneering research on T_R3-56 cells in cancer models would facilitate to reveal the phenotypic and functional characteristics of T_R3-56 cells. Therefore, this manuscript is helpful for further exploration of adaptive cellular immunoregulation and deserve publication.

Author Response

The Authors sincerely thank the Reviewer for appreciating the topic of the Review.