Single naive CD4+ T cells from a diverse repertoire produce different effector cell types during infection

Noah J. Tubo, Antonio J. Pagán, Justin J. Taylor, Ryan W Nelson, Jonathan L. Linehan, James M. Ertelt, Eric S. Huseby, Sing Sing Way, Marc Jenkins

Research output: Contribution to journalArticlepeer-review

314 Scopus citations

Abstract

A naive CD4+ T cell population specific for a microbial peptide:major histocompatibility complex II ligand (p:MHCII) typically consists of about 100 cells, each with a different T cell receptor (TCR). Following infection, this population produces a consistent ratio of effector cells that activate microbicidal functions of macrophages or help B cells make antibodies. We studied the mechanism that underlies this division of labor by tracking the progeny of single naive T cells. Different naive cells produced distinct ratios of macrophage and B cell helpers but yielded the characteristic ratio when averaged together. The effector cell pattern produced by a given naive cell correlated with the TCR-p:MHCII dwell time or the amount of p:MHCII. Thus, the consistent production of effector cell subsets by a polyclonal population of naive cells results from averaging the diverse behaviors of individual clones, which are instructed in part by the strength of TCR signaling.

Original languageEnglish (US)
Pages (from-to)785-796
Number of pages12
JournalCell
Volume153
Issue number4
DOIs
StatePublished - May 9 2013

Bibliographical note

Funding Information:
We thank J. Walter and R. Speier for technical assistance and T. Martin and the University of Minnesota Flow Cytometry Facility for cell sorting. This work was supported by grants from the National Institutes of Health (R01-AI39614, R37-AI27998, and R01-AI66018 to M.K.J.; T32-HD060536 to N.J.T.; T32-AI07313 to A.J.P.; F30-DK093242 to R.W.N.; R01-AI087830 and R01-AI100934 to S.S.W.; and T32-AI07313 to J.L.L.). This work was also supported by the Kunze Fellowship (to A.J.P.), the Irvington Fellowship from the Cancer Research Institute (to J.J.T.), and the Burroughs Wellcome Fund (to S.S.W.).

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