Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity
Ryan A. Zander,
Rahul Vijay,
Angela D. Pack,
Jenna J. Guthmiller,
Amy C. Graham,
Scott E. Lindner,
Ashley M. Vaughan,
Stefan H.I. Kappe,
Noah S. Butler
Affiliations
Ryan A. Zander
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Rahul Vijay
Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA
Angela D. Pack
Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA
Jenna J. Guthmiller
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Amy C. Graham
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Scott E. Lindner
Center for Malaria Research, Penn State University, University Park, PA 16802, USA; Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, USA; Center for Infectious Disease Research, Seattle, WA 98109, USA
Ashley M. Vaughan
Center for Infectious Disease Research, Seattle, WA 98109, USA
Stefan H.I. Kappe
Center for Infectious Disease Research, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98109, USA
Noah S. Butler
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Graduate Program in Biosciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA; Corresponding author
Summary: Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist. Unexpectedly, Th1-like memory cells exhibit phenotypic and functional features of Tfh cells during recall and provide potent B cell help and protection following transfer, characteristics that are enhanced following ligation of the T cell co-stimulatory receptor OX40. Our findings delineate critical functional attributes of Plasmodium-specific memory CD4 T cells and identify a host-specific factor that can be targeted to improve resolution of acute malaria and provide durable, long-term protection against Plasmodium parasite re-exposure. : Th1 CD4 T cells are widely described as terminally differentiated with a relatively reduced capacity to form memory or support humoral immunity. Using experimental malaria models, Zander et al. show that potent proliferative and B cell helper activity unexpectedly resides within the Plasmodium-specific Th1-like memory CD4 T cell compartment. Keywords: plasmodium, CD4 T cell, memory, T follicular helper cell, type 1 T helper cell, OX40, T-bet, Bcl-6
