Description:
<jats:title>Abstract</jats:title><jats:p>Regulatory and effector cell responses to <jats:italic>Plasmodium vivax</jats:italic>, the most common human malaria parasite outside Africa, remain understudied in naturally infected populations. Here, we describe peripheral CD4<jats:sup>+</jats:sup> T‐ and B‐cell populations during and shortly after an uncomplicated <jats:italic>P. vivax</jats:italic> infection in 38 continuously exposed adult Amazonians. Consistent with previous observations, we found an increased frequency in CD4<jats:sup>+</jats:sup>CD45RA<jats:sup>−</jats:sup>CD25<jats:sup>+</jats:sup>FoxP3<jats:sup>+</jats:sup> T regulatory cells that express the inhibitory molecule CTLA‐4 during the acute infection, with a sustained expansion of CD21<jats:sup>−</jats:sup>CD27<jats:sup>−</jats:sup> atypical memory cells within the CD19<jats:sup>+</jats:sup> B‐cell compartment. Both Th1‐ and Th2‐type subsets of CXCR5<jats:sup>+</jats:sup>ICOS<jats:sup>hi</jats:sup>PD‐1<jats:sup>+</jats:sup> circulating T follicular helper (cTfh) cells, which are thought to contribute to antibody production, were induced during <jats:italic>P. vivax</jats:italic> infection, with a positive correlation between overall cTfh cell frequency and IgG antibody titers to the <jats:italic>P. vivax</jats:italic> blood‐stage antigen MSP1<jats:sub>19</jats:sub>. We identified significant changes in cell populations that had not been described in human malaria, such as an increased frequency of CTLA‐4<jats:sup>+</jats:sup> T follicular regulatory cells that antagonize Tfh cells, and a decreased frequency of circulating CD24<jats:sup>hi</jats:sup>CD27<jats:sup>+</jats:sup> B regulatory cells in response to acute infection. In conclusion, we disclose a complex immunoregulatory network that is critical to understand how naturally acquired immunity develops in <jats:italic>P. vivax</jats:italic> malaria.</jats:p>