PP2A and Its Inhibitors in Helper T-Cell Differentiation and Autoimmunity

Protein phosphatase 2A (PP2A) is a highly complex heterotrimeric Ser/Thr phosphatase that regulates many cellular processes. The role of PP2A as a tumor suppressor has been extensively studied and reviewed. However, emerging evidence suggests PP2A constrains inflammatory responses and is important in autoimmune and neuroinflammatory diseases. Here, we reviewed the existing literature on the role of PP2A in T-cell differentiation and autoimmunity. We have also discussed the modulation of PP2A activity by endogenous inhibitors and its small-molecule activators as potential therapeutic approaches against autoimmunity.

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Role of CD5 expression on TCRγδ T cell-differentiation and development of chronic intestinal inflammation

Gastroenterology ◽

10.1016/s0016-5085(01)82566-x ◽

2001 ◽

Vol 120 (5) ◽

pp. A517-A517

Author(s):

A MIZOGUCHI ◽

E MIZOGUCHI ◽

Y DEJONG ◽

H TAKEDATSU ◽

F PREFFER ◽

...

Keyword(s):

Cell Differentiation ◽

T Cell ◽

Intestinal Inflammation ◽

T Cell Differentiation ◽

Chronic Intestinal Inflammation

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The role of thymic accessory cells in cytokine production and in the intra-thymic T cell differentiation pathway

Memórias do Instituto Oswaldo Cruz ◽

10.1590/s0074-02761987000600006 ◽

1987 ◽

Vol 82 (suppl 2) ◽

pp. 23-28

Author(s):

Martine Papiernik

Keyword(s):

Cell Differentiation ◽

T Cell ◽

Cytokine Production ◽

T Cell Differentiation ◽

Accessory Cells

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Role of PD-1 during effector CD8 T cell differentiation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1718217115 ◽

2018 ◽

Vol 115 (18) ◽

pp. 4749-4754 ◽

Cited By ~ 92

Author(s):

Eunseon Ahn ◽

Koichi Araki ◽

Masao Hashimoto ◽

Weiyan Li ◽

James L. Riley ◽

...

Keyword(s):

T Cells ◽

Cell Differentiation ◽

T Cell ◽

Viral Infection ◽

Cd8 T Cells ◽

Cell Epitope ◽

Cd8 T Cell ◽

T Cell Differentiation ◽

Lcmv Infection

PD-1 (programmed cell death-1) is the central inhibitory receptor regulating CD8 T cell exhaustion during chronic viral infection and cancer. Interestingly, PD-1 is also expressed transiently by activated CD8 T cells during acute viral infection, but the role of PD-1 in modulating T cell effector differentiation and function is not well defined. To address this question, we examined the expression kinetics and role of PD-1 during acute lymphocytic choriomeningitis virus (LCMV) infection of mice. PD-1 was rapidly up-regulated in vivo upon activation of naive virus-specific CD8 T cells within 24 h after LCMV infection and in less than 4 h after peptide injection, well before any cell division had occurred. This rapid PD-1 expression by CD8 T cells was driven predominantly by antigen receptor signaling since infection with a LCMV strain with a mutation in the CD8 T cell epitope did not result in the increase of PD-1 on antigen-specific CD8 T cells. Blockade of the PD-1 pathway using anti–PD-L1 or anti–PD-1 antibodies during the early phase of acute LCMV infection increased mTOR signaling and granzyme B expression in virus-specific CD8 T cells and resulted in faster clearance of the infection. These results show that PD-1 plays an inhibitory role during the naive-to-effector CD8 T cell transition and that the PD-1 pathway can also be modulated at this stage of T cell differentiation. These findings have implications for developing therapeutic vaccination strategies in combination with PD-1 blockade.

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