Comparative analysis of activation phenotype, proliferation, and IFN-gamma production by spleen NK1.1(+) and NK1.1(-) T cells during Plasmodium chabaudi AS malaria.
The NK1.1 molecule participates in NK, NKT, and T-cell activation, contributing to IFN-gamma production and cytotoxicity. To characterize the early immune response to Plasmodium chabaudi AS, spleen NK1.1(+) and NK1.1(-) T cells were compared in acutely infected C57BL/6 mice. The first parasitemia peak in C57BL/6 mice correlated with increase in CD4(+)NK1.1(+)TCR-alphabeta(+), CD8(+)NK1.1(+)TCR-alphabeta(+), and CD4(+)NK1.1(-)TCR-alphabeta(+) cell numbers per spleen, where a higher increment was observed for NK1.1(+) T cells compared to NK1.1(-) T cells. According to the ability to recognize the CD1d-alpha-GalCer tetramer, CD4(+)NK1.1(+) cells in 7-day infected mice were not predominantly invariant NKT cells. At that time, nearly all NK1.1(+) T cells and around 30% of NK1.1(-) T cells showed an experienced/activated (CD44(HI)CD69(HI)CD122(HI)) cell phenotype, with high expression of Fas and PD-L1 correlating with their low proliferative capacity. Moreover, whereas IFN-gamma production by CD4(+)NK1.1(+) cells peaked at day 4 p.i., the IFN-gamma response of CD4(+)NK1.1(-) cells continued to increase at day 5 of infection. We also observed, at day 7 p.i., 2-fold higher percentages of perforin(+) cells in CD8(+)NK1.1(+) cells compared to CD8(+)NK1.1(-) cells. These results indicate that spleen NK1.1(+) and NK1.1(-) T cells respond to acute P. chabaudi malaria with different kinetics in terms of activation, proliferation, and IFN-gamma production.
Muxel
Sandra Marcia
SM
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. sandrammuxel@gmail.com
Freitas do Rosário
Ana Paula
AP
Sardinha
Luiz Roberto
LR
Castillo-Méndez
Sheyla Inés
SI
Zago
Cláudia Augusta
CA
Rodriguez-Málaga
Sérgio Marcelo
SM
Alvarez Mosig
José Maria
JM
D'Império Lima
Maria Regina
MR
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000950:Antigens, Ly / Q000096:biosynthesis; D049109:Cell Proliferation; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000096:biosynthesis; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D016788:Plasmodium chabaudi / Q000276:immunology* / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology
D015703:Antigens, CD; D000950:Antigens, Ly; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D007371:Interferon-gamma