Allogeneic differences in the dependence on CD4+ T-cell help for virus-specific CD8+ T-cell differentiation.
CD4(+) T-cell help enables antiviral CD8(+) T cells to differentiate into fully competent memory cells and sustains CD8(+) T-cell-mediated immunity during persistent virus infection. We recently reported that mice of C57BL/6 and C3H strains differ in their dependence on CD28 and CD40L costimulation for long-term control of infection by polyoma virus, a persistent mouse pathogen. In this study, we asked whether mice of these inbred strains also vary in their requirement for CD4(+) T-cell help for generating and maintaining polyoma virus-specific CD8(+) T cells. CD4(+) T-cell-depleted C57BL/6 mice mounted a robust antiviral CD8(+) T-cell response during acute infection, whereas unhelped CD8(+) T-cell effectors in C3H mice were functionally impaired during acute infection and failed to expand upon antigenic challenge during persistent infection. Using (C57BL/6 x C3H)F(1) mice, we found that the dispensability for CD4(+) T-cell help for the H-2(b)-restricted polyoma virus-specific CD8(+) T-cell response during acute infection extends to the H-2(k)-restricted antiviral CD8(+) T cells. Our findings demonstrate that dependence on CD4(+) T-cell help for antiviral CD8(+) T-cell effector differentiation can vary among allogeneic strains of inbred mice.
Kemball
Christopher C
CC
Department of Pathology, Emory University School of Medicine, Woodruff Memorial Research Building, Room 7307, 101 Woodruff Circle, Atlanta, GA 30322, USA.
Szomolanyi-Tsuda
Eva
E
Lukacher
Aron E
AE
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D005260:Female; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000276:immunology* / Q000821:virology; D013045:Species Specificity; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology; D010948:Viral Plaque Assay