CD8 regulatory T cells: Friend or foe in routes of infection

• Grant number: 19/12431-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2019
• End date: September 30, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jean Pierre Schatzmann Peron
• Grantee: Nagela Ghabdan Zanluqui
• Supervisor: Laura Kate Mackay
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Melbourne, Australia
• Associated to the scholarship: 16/07371-2 - Characterization of the role of T CD8+ lymphocytes in Zika virus infection, BP.DR

Abstract

CD8 effector T cells are important in control viruses' infections and cancer growth using cytolytic mechanisms as granzyme and perforin secretion, Fas-FasL interaction and by IFN-³ and TNF-± cytokines. Differently of these cells, CD8 regulatory T (CD8regs) cells have potent suppressive and regulatory functions as compared to CD4regs cells. These activities can occur by Fas-FasL interaction, by TGF-² and IL-10 secretion, or by expression of some suppressive markers as CD39. These CD8regs cells can express many regulatory/suppressors markers, such as CD122, CTLA4, PD-1, CD103, and Foxp3 among others. CD8regs cells are involved in control deleterious response after transplantation suppressing immune response against the graft. On the other hand, during infections these cells seems to suppress immune response against the virus what result in increase of virus replication and establishment of infection. Interestingly, these cells can be related to the maintenance of tolerance during pregnancy, and in vitro CD8regs cells can be generated after incubation with trophoblasts, besides that, deffects in CD8regs cells in the decidua can cause damage to the placenta and result in restriction of fetal growth. In these way, CD8reg cells are important in many different scenarios behaving as Friend in some cases, or Foe in others. Here we will characterize if there are CD8reg cells in skin and, evaluate the role of these cells in skin, uterus and placenta at the first steps of viral infection, since Zika virus (ZIKV) use these both as route for its infection. Therefore, this project aims to contribute to the PhD project (2016/07371-2) whose aim is to evaluate the role of CD8 T cells during ZIKV infection. These experiments will be conducted in a cutting-edge laboratory led by Professor Laura Mackay (Melbourne - AUS), who has extensive experience in studying the CD8 resident memory T cells in skin models. This research will contribute to a better understanding of the immunobiology of CD8regs cells in the congenital infection caused by ZIKV, and perhaps discover tools for the control of viral replication and congenital ZIKV transmission.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FRIZZELL, H.; FONSECA, R.; CHRISTO, S. N.; EVRARD, M.; CRUZ-GOMEZ, S.; ZANLUQUI, N. G.; VON SCHEIDT, B.; FREESTONE, D.; PARK, S. L.; MCWILLIAM, H. E. G.; et al. Organ-specific isoform selection of fatty acid-binding proteins in tissue-resident lymphocytes. SCIENCE IMMUNOLOGY, v. 5, n. 46, APR 2020. (19/12431-2)

FONSECA, RAISSA; BURN, THOMAS N.; GANDOLFO, LUKE C.; DEVI, SAPNA; PARK, SIMONE L.; OBERS, ANDREAS; EVRARD, MAXIMILIEN; CHRISTO, SUSAN N.; BUQUICCHIO, FRANK A.; LAREAU, CALEB A.; et al. Runx3 drives a CD8(+) T cell tissue residency program that is absent in CD4(+) T cells. NATURE IMMUNOLOGY, v. 23, n. 8, p. 24-pg., 2022-07-26. (19/12431-2)