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Immunity to Malaria and Vaccine Strategies

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Front. Immunol. | doi: 10.3389/fimmu.2018.02277

NK1.1 expression defines a population of CD4+ effector T cells displaying Th1 and Tfh cell properties that support early antibody production during Plasmodium yoelii infection

 Daniel J. Wikenheiser1, Susie L. Brown1, Juhyung Lee1 and  Jason S. Stumhofer1*
  • 1University of Arkansas for Medical Sciences, United States

Early plasmablast induction is a hallmark of Plasmodium infection and is thought to contribute to the control of acute parasite burden. Although long understood to be a T-cell dependent phenomenon, regulation of early plasmablast differentiation, however, is poorly understood. Here, we identify a population of CD4+ T cells that express the innate NK cell marker NK1.1 as an important source of T cell help for early plasmablast and parasite-specific Ab production. Interestingly, NK1.1+ CD4+ T cells arise from conventional, naive NK1.1- CD4+ T cells, and their generation is independent of CD1d but critically reliant on MHC-II. CD4+ T cells that express NK1.1 early after activation produce IFN- and IL-21, and express the follicular helper T (Tfh) cell markers ICOS, PD-1 and CXCR5 more frequently than NK1.1- CD4+ T cells. Further analysis of this population revealed that NK1.1+ Tfh-like cells were more regularly complexed with plasmablasts than NK1.1- Tfh-like cells. Ultimately, depletion of NK1.1+ cells impaired class-switched parasite-specific antibody production during early Plasmodium yoelii infection. Together, these data suggest that expression of NK1.1 defines a population of rapidly expanding effector CD4+ T cells that specifically promote plasmablast induction during Plasmodium infection and represent a subset of T cells whose modulation could promote effective vaccine design.

Keywords: Malaria, T follicular helper cell (TFH), antibody, NK1.1+ cells, plasmablast

Received: 28 Jun 2018; Accepted: 13 Sep 2018.

Edited by:

Kevin Couper, University of Manchester, United Kingdom

Reviewed by:

Tracey Lamb, University of Utah, United States
Robin Stephens, The University of Texas Medical Branch at Galveston, United States  

Copyright: © 2018 Wikenheiser, Brown, Lee and Stumhofer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Jason S. Stumhofer, University of Arkansas for Medical Sciences, Little Rock, United States, jstumhofer@uams.edu