Follicular CD4 T Cells Tutor CD8 Early Memory Precursors: An Initiatory Journey to the Frontier of B Cell Territory

摘要

class="head no_bottom_margin" id="sec1title">IntroductionFollowing antigen activation, a naive CD8 cell subset undergoes strong clonal expansion, generating a heterogeneous population of activated cells that is dominated, at the peak of expansion, by short-lived CD8 effectors (). This expansion is followed by a phase of drastic contraction through massive apoptosis. A few cells survive this contraction phase and eventually become highly competent memory cells (). Precisely when and how these memory precursors are generated is largely unknown, however, and so are the subsequent steps of their maturation into fully functional memory cells. Help signals from CD4⁺ T cells are clearly required throughout the memory precursor (MPEC) maturation process (). However, CD4⁺ T cells form a heterogeneous group that includes several subsets with different functional properties. FoxP3⁺ regulatory CD4⁺ T cells have been shown to favor memory precursor maturation by limiting exposure to interleukin (IL)-2 and by providing inhibitory signals (, ), but this is probably only one facet of the complex and multifaceted help provided by CD4⁺ T cells to memory precursors (, ). Here, we show that, as early as 2 days after antigen priming, very early memory precursors can be identified by their expression of the chemokine receptor CXCR5. These CXCR5⁺ precursors migrate to the junction between T and B cell zones, where they receive critical help from follicular CD4⁺ T cells (Tfh), a specialized CD4⁺ T cell subset hitherto considered as exclusive B cell helpers (, ). Tfh enable these CXCR5⁺ precursors to become highly competent memory cells.