title: KLRG1+NKG2A+ CD8 T cells mediate protection and participate in memory responses during γ-herpesvirus infection.
abstract: Functional CD8 T cell effector and memory responses are generated and maintained during murine γ-herpesvirus 68 (γHV68) persistent infection despite continuous presentation of viral lytic Ags. However, the identity of the CD8 T cell subpopulations that mediate effective recall responses and that can participate in the generation of protective memory to a γ-herpesvirus infection remains unknown. During γHV68 persistence, ∼75% of γHV68-specific CD8 T cells coexpress the NK receptors killer cell lectin-like receptor G1 (KLRG1) and NKG2A. In this study, we take advantage of this unique phenotype to analyze the capacity of CD8 T cells expressing or not expressing KLRG1 and NKG2A to mediate effector and memory responses. Our results show that γHV68-specific KLRG1(+)NKG2A(+) CD8 T cells have an effector memory phenotype as well as characteristics of polyfunctional effector cells such us IFN-γ and TNF-α production, killing capacity, and are more efficient at protecting against a γHV68 challenge than their NKG2A(-)KLRG1(-) counterparts. Nevertheless, γHV68-specific NKG2A(+)KLRG1(+) CD8 T cells express IL-7 and IL-15 receptors, can survive long-term without cognate Ag, and subsequently mount a protective response during antigenic recall. These results highlight the plasticity of the immune system to generate protective effector and proliferative memory responses during virus persistence from a pool of KLRG1(+)NKG2A(+) effector memory CD8 T cells.
authors.affiliation: Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Cush
authors.forename: Emilio
authors.initials: E
authors.lastname: Flaño
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D006566:Herpesviridae Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007156:Immunologic Memory; D016130:Immunophenotyping; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000008:administration & dosage / Q000096:biosynthesis* / Q000502:physiology; D011971:Receptors, Immunologic / Q000008:administration & dosage / Q000096:biosynthesis* / Q000502:physiology; D018144:Rhadinovirus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D017735:Virus Latency / Q000276:immunology
chemical_list: C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic