WHAT IS IMMUNE TOLERANCE

The mechanism of T cell tolerance. Central tolerance of T cells occurs in the thymus. Hematopoietic lymphoid progenitors migrate to cortex, where they are screened by thymic epithelia cells and develop into CD4⁺CD8⁺ double-positive (DP) thymocytes expressing the T-cell antigen receptor (TCR). DP cells migrate to the medulla. After screening for the ability to bind to self-peptide-associated major histocompatibility complex class I (MHC-I) or MHC class II (MHC-II) molecules on the antigen-presenting cell (APC) surface, DP cells develop into CD4⁺CD8⁺ DP thymocytes expressing the TCR. Screening for binding capacity of molecules culminating in Treg CD8⁺ T cells, and CD4⁺ T cells migrate to lymph node to undergo peripheral tolerance.

Peripheral tolerance mechanisms, such as exhaustion, deletion, anergy, and regulation are mainly relied upon to suppress the activity of self-reactive T cells. Exhaustion and deletion are realized through inhibiting cell function or proliferative capacity of effector T cell and apoptosis. Anergy describes a state of hyporesponsiveness of naive T cells to TCR stimuli after exposure to antigen. Treg cells regulate by inhibiting effector T cell activity and B cell proliferation via interleukin-(IL)-10, Transforming growth factor-β (TGF-beta), and IL-35.