Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load

Modulation of CD4(+) T Cell-Dependent Specific Cytotoxic CD8(+) T Cells Differentiation and Proliferation by the Timing of Increase in the Pathogen Load

Author Tzelepis, Fanny Autor UNIFESP Google Scholar
Persechini, Pedro M. Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do Rio de Janeiro (UFRJ)
Abstract Background. Following infection with viruses, bacteria or protozoan parasites, naive antigen-specific CD8(+) T cells undergo a process of differentiation and proliferation to generate effector cells. Recent evidences suggest that the timing of generation of specific effector CD8(+) T cells varies widely according to different pathogens. We hypothesized that the timing of increase in the pathogen load could be a critical parameter governing this process. Methodology/Principal Findings. Using increasing doses of the protozoan parasite Trypanosoma cruzi to infect C57BL/6 mice, we observed a significant acceleration in the timing of parasitemia without an increase in mouse susceptibility. in contrast, in CD8 deficient mice, we observed an inverse relationship between the parasite inoculum and the timing of death. These results suggest that in normal mice CD8(+) T cells became protective earlier, following the accelerated development of parasitemia. the evaluation of specific cytotoxic responses in vivo to three distinct epitopes revealed that increasing the parasite inoculum hastened the expansion of specific CD8(+) cytotoxic T cells following infection. the differentiation and expansion of T. cruzi-specific CD8(+) cytotoxic T cells is in fact dependent on parasite multiplication, as radiation-attenuated parasites were unable to activate these cells. We also observed that, in contrast to most pathogens, the activation process of T. cruzi-specific CD8(+) cytotoxic T cells was dependent on MHC class II restricted CD4(+) T cells. Conclusions/Significance. Our results are compatible with our initial hypothesis that the timing of increase in the pathogen load can be a critical parameter governing the kinetics of CD4(+) T cell-dependent expansion of pathogen-specific CD8(+) cytotoxic T cells.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Millennium Institute for Vaccine Development and Technology
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number Millennium Institute for Vaccine Development and Technology: CNPq - 420067/2005-1
Date 2007-04-25
Published in Plos One. San Francisco: Public Library Science, v. 2, n. 4, 9 p., 2007.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 9
Origin http://dx.doi.org/10.1371/journal.pone.0000393
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000207445600007
URI http://repositorio.unifesp.br/handle/11600/29673

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