title: MHC class Ib-restricted CD8 T cells differ in dependence on CD4 T cell help and CD28 costimulation over the course of mouse polyomavirus infection.
abstract: We recently identified a protective MHC class Ib-restricted CD8 T cell response to infection with mouse polyomavirus. These CD8 T cells recognize a peptide from aa 139-147 of the VP2 viral capsid protein bound to the nonpolymorphic H-2Q9 molecule, a member of the Qa-2 family of β(2)m-associated MHC class Ib molecules. Q9:VP2.139-specific CD8 T cells exhibit an unusual inflationary response characterized by a gradual expansion over 3 mo followed by a stable maintenance phase. We previously demonstrated that Q9:VP2.139-specific CD8 T cells are dependent on Ag for expansion, but not for long-term maintenance. In this study, we tested the hypothesis that the expansion and maintenance components of the Q9:VP2.139-specific T cell response are differentially dependent on CD4 T cell help and CD28 costimulation. Depletion of CD4(+) cells and CD28/CD40L blockade impaired expansion of Q9:VP2.139-specific CD8 T cells, and intrinsic CD28 signaling was sufficient for expansion. In contrast, CD4 T cell insufficiency, but not CD28/CD40L blockade, resulted in a decline in frequency of Q9:VP2.139-specific CD8 T cells during the maintenance phase. These results indicate that the Q9:VP2.139-specific CD8 T cell response to mouse polyomavirus infection depends on CD4 T cell help and CD28 costimulation for inflationary expansion, but only on CD4 T cell help for maintenance.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Hofstetter
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Ford
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Sullivan
authors.forename: Jarad J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Annette
authors.initials: A
authors.lastname: Hadley
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Aron E
authors.initials: AE
authors.lastname: Lukacher
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D060966:Clonal Selection, Antigen-Mediated; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D007668:Kidney / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011120:Polyomavirus / Q000302:isolation & purification; D027601:Polyomavirus Infections / Q000276:immunology* / Q000821:virology; D012469:Salivary Glands / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology
chemical_list: D018106:CD28 Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C032907:Q surface antigens; D023201:CD40 Ligand