title: Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection.
abstract: BACKGROUND
  For a long time, the role of CD8(+) T cells in blood-stage malaria was not considered important because erythrocytes do not express major histocompatibility complex (MHC) class I proteins. While recent evidences suggest that CD8(+) T cells may play an important role during the erythrocytic phase of infection by eliminating parasites, CD8(+) T cells might also contribute to modulate the host response through production of regulatory cytokines. Thus, the role of CD8(+) T cells during blood-stage malaria is unclear. Here, we report the phenotypic profiling of CD8(+) T cells subsets from patients with uncomplicated symptomatic P. vivax malaria.
  
  
  METHODS
  Blood samples were collected from 20 Plasmodium vivax-infected individuals and 12 healthy individuals. Immunophenotyping was conducted by flow cytometry. Plasma levels of IFN-γ, TNF-α and IL-10 were determined by ELISA/CBA. Unpaired t-test or Mann-Whitney test was used depending on the data distribution.
  
  
  RESULTS
  P. vivax-infected subjects had lower percentages and absolute numbers of CD8(+)CD45RA(+) and CD8(+)CD45RO(+) T cells when compared to uninfected individuals (p ≤ 0.0002). A significantly lower absolute number of circulating CD8(+)CD45(+)CCR7(+) cells (p = 0.002) was observed in P. vivax-infected individuals indicating that infection reduces the number of central memory T cells. Cytokine expression was significantly reduced in the naïve T cells from infected individuals compared with negative controls, as shown by lower numbers of IFN-γ(+) (p = 0.001), TNF-α(+) (p < 0.0001) and IL-10(+) (p < 0.0001) CD8(+) T cells. Despite the reduction in the number of CD8(+) memory T cells producing IFN-γ (p < 0.0001), P. vivax-infected individuals demonstrated a significant increase in memory CD8(+)TNF-α(+) (p = 0.016) and CD8(+)IL-10(+) (p = 0.004) cells. Positive correlations were observed between absolute numbers of CD8(+)IL-10(+) and numbers of CD8(+)IFN-γ(+) (p < 0.001) and CD8(+)TNF-α(+) T cells (p ≤ 0.0001). Finally, an increase in the plasma levels of TNF-α (p = 0.017) and IL-10 (p = 0.006) and a decrease in the IFN-γ plasma level (p <0.0001) were observed in the P. vivax-infected individuals.
  
  
  CONCLUSIONS
  P. vivax infection reduces the numbers of different subsets of CD8(+) T cells, particularly the memory cells, during blood-stage of infection and enhances the number of CD8(+) memory T cells expressing IL-10, which positively correlates with the number of cells expressing TNF-α and IFN-γ.
authors: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. nataliasatchiko@gmail.com.
authors: Natália Satchiko
authors: NS
authors: Hojo-Souza
authors: Centro de Pesquisa em Medicina Tropical, Porto Velho, Rondônia, Brazil. dbpfall@gmail.com.
authors: Dhelio Batista
authors: DB
authors: Pereira
authors: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. liviasap@gmail.com.
authors: Lívia Silva Araújo
authors: LS
authors: Passos
authors: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. pedrogazzinelli@yahoo.com.br.
authors: Pedro Henrique
authors: PH
authors: Gazzinelli-Guimarães
authors: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. marianascardoso@yahoo.com.br.
authors: Mariana Santos
authors: MS
authors: Cardoso
authors: Centro de Pesquisa em Medicina Tropical, Porto Velho, Rondônia, Brazil. maurotada@gmail.com.
authors: Mauro Shugiro
authors: MS
authors: Tada
authors: Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil. graziela.zanini@ipec.fiocruz.br.
authors: Graziela Maria
authors: GM
authors: Zanini
authors: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. daniella@icb.ufmg.br.
authors: Daniella Castanheira
authors: DC
authors: Bartholomeu
authors: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. fujiwara@icb.ufmg.br.
authors: Ricardo Toshio
authors: RT
authors: Fujiwara
authors: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. lilacerdabueno@gmail.com.
authors: Lilian Lacerda
authors: LL
authors: Bueno
mesh_terms: D000328:Adult; D000368:Aged; D001772:Blood Cell Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016780:Malaria, Vivax / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010966:Plasmodium vivax / Q000276:immunology*; D055815:Young Adult
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