Restoring function in exhausted CD8 T cells during chronic viral infection

Barber, D. L. et al., Nature, (2006) 439, 682-687

Speaker：林雅葶                           Date：2006/05/03, 13:10~14:00

Commentator：王憲威 老師                 Place：Room 601

Abstract

The cytotoxic T lymphocytes can destroy infected cells and constitute the antigen activated cellular immunity to control infection of many intracellular pathogens. Memory CD8 T cells generated after an acute viral infection are highly functional and constitute an important component of protective immunity. In contrast, chronic infections are often characterized by varying degrees of functional impairment of virus-specific CD8 T cell responses that are accounted for the inability of the host to eliminate the persisting pathogen. Using the lymphocytic choriomeningitis virus (LCMV)¹ infection model to establish either acute or chronic infection by Armstrong and Clone 13, respectively. Barber et al.² found the programmed death-1 (PD-1), an inhibitory receptor of the CD28 family³, was selectively upregulated by the exhausted T cells. Blockade of this inhibitory receptor with its ligand, PD-L1 is particularly effective in restoring impaired CD8 T cells, enhancing viral control and T cell responses during chronic infection. Furthermore, blockade of the PD-1/PD-L1 inhibitory pathway would enhance CD8 T cell responses in the absence of CD4 T cell help. Furthermore, the PD-1 effect is different from that of CTLA-4. It was concluded blockade of PD-L1 has a restoring mechanism of T-cell exhaustion and define a potentially effective immunological strategy for the treatment of chronic viral infections.

References

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2.      Barber, D. L. et al., (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature, 439, 682-687

3.      Chen, L., (2004) Co-inhibitory molecules of the B7–CD28 family in the control of T-cell immunity. Nat. Rev. Immunol. 4, 336-347