An early commitment to expression of a particular TCRVbeta chain on CD8(+) T cells responding to attenuated Plasmodium berghei sporozoites is maintained following challenge with infectious sporozoites.
Protection induced by irradiated Plasmodium berghei sporozoites (Pbgamma-spz) in mice is linked to CD8(+) T cells specific for exo-erythrocytic-stage Ags, and intrahepatic memory CD8(+) T cells are associated with protracted protection. However, the Ag specificity of the protective CD8(+) T cells remains largely unknown. In this study, we characterized the TCR Vbeta usage by intrahepatic CD8(+) T cells during gamma-spz immunization and after the challenge with infectious Pb sporozoites. The repertoire of naïve (T(N)) and central memory (T(CM)) CD8(+) T cells was diverse and conserved between individual mice, and did not change with immunization. In contrast, preferential usage of one or more TCR Vbeta subset was observed in effector memory (T(EM)) CD8(+) T cells after immunization. The expanded TCR Vbeta varied between individual mice but Vbeta4, 6, 7, 8.3, 9 and 11 were the most frequently expressed. In addition, there was a correlation in the TCR Vbeta usage by gamma-spz-induced CD8(+) T(EM) in the liver and blood of individual mice. The expansion pattern of blood CD8(+) T(EM) did not change with challenge and remained the same for 8 weeks thereafter. These results demonstrate that immunization with gamma-spz skews the TCR Vbeta repertoire of CD8(+) T(EM), and commitment to a particular TCR Vbeta expression is maintained long-term.
Lumsden
J M
JM
Department of Cellular Immunology, Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Cranmer
M A
MA
Krzych
U
U
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005720:Gamma Rays; D007114:Immunization; D008099:Liver / Q000378:metabolism; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D010962:Plasmodium berghei / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D034101:Sporozoites / Q000276:immunology* / Q000528:radiation effects; D014613:Vaccines, Attenuated / Q000276:immunology
D017780:Malaria Vaccines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014613:Vaccines, Attenuated