| Memory CD8 T cells comprise a critical component of antiviral immunity because of their capacity to proliferate and exert effector activity faster than naive T cells upon antigen encounter. During persistent viral infection, memory CD8 T cells repetitively encounter viral antigen and must maintain a delicate balance between limiting viral replication and minimizing immunopathology. In this work, we use polyoma virus (PyV), a persisent pathogen capable of tumor induction, to study memory CD8 T cell function during a persistent viral infection.; We demonstrated that PyV-specific CD8 T cells specifically eliminate viral peptide-pulsed donor spleen cells within minutes after adoptive transfer in both acute and persistent infection, and do so via a perforin-dependent mechanism. These findings provide direct evidence that memory CD8 T cells are capable of rapid in vivo effector function.; The recent propensity to classify heterogeneous memory T cell populations into discrete subsets based on either phenotypic or functional differences has become increasingly complex as greater numbers of cell surface molecules and different infection models are studied. Several canonical classification markers do not apply to memory CD8 T cells from persistent infections. In mice infected by PyV, the majority of persistent antiviral CD8 T cells express the inhibitory NK cell receptor CD94/NKG2A. We found that PyV-specific CD8 T cells that express CD94/NKG2A preferentially proliferate during the persistent phase and upon antigen-specific recall; this proliferation was dependent on cognate antigen both in vitro and in vivo. Additionally, CD94/NKG2A + PyV-specific CD8 T cells produce significantly more IL-2 upon ex vivo antigen stimulation. Identification of proliferation-competent subpopulations of memory CD8 T cells should prove valuable in designing therapeutic vaccination strategies for persistent viral infections.; Although CD8 T cells are essential for rejection of PyV-induced tumors and perforin is necessary for efficient in vivo cytotoxicity, we found that perforin-deficient mice infected with PyV did not differ from wild type mice with respect to acute and persistent viremia, CD8 T cell homeostasis, nor tumorigenesis. Surprisingly, elimination of both the perforin and Fas/FasL pathways did not lead to tumor formation indicating that PyV-induced tumorigenesis requires a complex and multi-factorial inhibition of the immune system. |
