Comparative Analysis of Activation Phenotype, Proliferation, and IFN-gama Production by Spleen NK1.1+ and NK1.1- T cells during Plasmodium chabaudi AS.

• Grant number: 10/00749-3
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: March 01, 2010
• End date: August 31, 2010
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Maria Regina D'Império Lima
• Grantee: Maria Regina D'Império Lima
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The NK1.1 molecule participates in NK, NKT and T cell activation, contributing to IFN-³ 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±²+, CD8+NK1.1+TCR±²+ and CD4+NK1.1-TCR±²+ 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-a-Gal-Cer 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 (CD44HICD69HICD122HI) cell phenotype, with high expression of Fas and PD-L1 correlating with their low proliferative capacity. Moreover, whereas IFN-³ production by CD4+NK1.1+ cells peaked at day 4 p.i., the IFN-³ 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 ativation, proliferation and IFN-³ production. (AU)