Human T Regulatory Cells Can Use the Perforin Pathway to Cause Autologous Target Cell Death

Immunity 21, 589–601, 2004

Speaker : 賴柏吟                      Time : 15:10~16:00, 29 Dec 2004

Commentator : 徐麗君 博士            Place : Room 601

Abstract

Human T regulatory cells (Treg) are a subset of T cells that function mostly to inhibit immunopathology or autoimmune disease. Different population of Treg cells have been identified, including CD4^＋CD25^＋ natural Treg and CD4^＋ adaptive Treg.⁽¹⁾ The perforin/granzyme pathway limited to CTL and NK cells, is a critical mechanism of   host defense for viral clearance and tumor cell killing. Although human CD4^＋ T cells have been shown to express perforin and granzyme, the functional significance of the granule exocytosis pathway in these cells has not yet been clearly established in Treg cells. Since perforin/granzyme-mediated target cell death requires cell contact, the authors investigated whether Treg cells are armed with cytotoxic granules. In this report, the authors demonstrated that natural Treg cells express predominantly granzyme A, but adaptive Treg cells express granzyme B. Both Treg subsets can use the perforin/granzyme pathway to promote autologous immune cell death, including CD4^＋ and CD8^＋ T cells, CD14^＋ monocytes, and dendritic cells.⁽²⁾ Hemophagocytic lymphohistiocytosis patients, who lack perforin or other granule exocytosis associated proteins, are defective in shutdown the immune response against infections.⁽³⁾ Since Treg cells play a role in suppressing immune response, this clinical evidence further implies that Treg cells may reach their function via perforin/granzyme pathway.

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