PD-1 Co-inhibitory and OX40 Co-stimulatory Crosstalk Regulates Helper T Cell Differentiation and Anti-Plasmodium Humoral Immunity. Other Scholarly Work

Zander, Ryan A, Obeng-Adjei, Nyamekye, Guthmiller, Jenna J et al. (2015). PD-1 Co-inhibitory and OX40 Co-stimulatory Crosstalk Regulates Helper T Cell Differentiation and Anti-Plasmodium Humoral Immunity. . 17(5), 628-641. 10.1016/j.chom.2015.03.007

cited authors

  • Zander, Ryan A; Obeng-Adjei, Nyamekye; Guthmiller, Jenna J; Kulu, Divine I; Li, Jun; Ongoiba, Aissata; Traore, Boubacar; Crompton, Peter D; Butler, Noah S

fiu authors

abstract

  • The differentiation and protective capacity of Plasmodium-specific T cells are regulated by both positive and negative signals during malaria, but the molecular and cellular details remain poorly defined. Here we show that malaria patients and Plasmodium-infected rodents exhibit atypical expression of the co-stimulatory receptor OX40 on CD4 T cells and that therapeutic enhancement of OX40 signaling enhances helper CD4 T cell activity, humoral immunity, and parasite clearance in rodents. However, these beneficial effects of OX40 signaling are abrogated following coordinate blockade of PD-1 co-inhibitory pathways, which are also upregulated during malaria and associated with elevated parasitemia. Co-administration of biologics blocking PD-1 and promoting OX40 signaling induces excessive interferon-gamma that directly limits helper T cell-mediated support of humoral immunity and decreases parasite control. Our results show that targeting OX40 can enhance Plasmodium control and that crosstalk between co-inhibitory and co-stimulatory pathways in pathogen-specific CD4 T cells can impact pathogen clearance.

publication date

  • May 1, 2015

keywords

  • Animals
  • Cell Differentiation
  • Gene Expression Regulation
  • Humans
  • Immunity, Humoral
  • Malaria
  • Mice
  • Plasmodium
  • Programmed Cell Death 1 Receptor
  • Receptors, OX40
  • T-Lymphocytes, Helper-Inducer

Digital Object Identifier (DOI)

Medium

  • Print-Electronic

start page

  • 628

end page

  • 641

volume

  • 17

issue

  • 5