Antigen-stimulated CD4 T-cell expansion is inversely and log-linearly related to precursor number

Juan Quiel, Stephane Caucheteux, Arian Laurence, Nevil J. Singh, Gennady Bocharov, Shlomo Z. Ben-Sasson, Zvi Grossman, William E. Paul

Research output: Contribution to journalArticlepeer-review

Abstract

Antigen-driven expansion of specific CD4 T cells diminishes, on a per cell basis, as infused cell number increases. There is a linear relation between log precursor number and log factor of expansion (FE), with a slope of ∼-0.5 over a range from 3 to 30,000 precursors. Cell number dependence of FE is observed at low precursor number, implying that the underlying process physiologically regulates antigen-driven T-cell expansion. FE of small numbers of transgenic precursors is not significantly affected by concomitant responses of large numbers of cells specific for different antigens. Increasing antigen amount or exogenous IL-2, IL-7, or IL-15 does not significantly affect FE, nor does FE depend on Fas, TNF-α receptor, cytotoxic T-lymphocyte antigen-4, IL-2, or IFN-γ. Small numbers of Foxp3-deficient T-cell receptor transgenic cells expand to a greater extent than do large numbers, implying that this effect is not mediated by regulatory T cells. Increasing dendritic cell number does result in larger FE, but the quantitative relation between FE and precursor number is not abrogated. Although not excluding competition for peptide/MHC complexes as an explanation, fall in FE with increasing precursor number could be explained by a negative feedback in which increasing numbers of responding cells in a cluster inhibit the expansion of cells of the same specificity within that cluster.

Original languageEnglish
Pages (from-to)3312-3317
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number8
DOIs
StatePublished - 22 Feb 2011
Externally publishedYes

Funding

FundersFunder number
National Institute of Allergy and Infectious DiseasesZIAAI000926

    Keywords

    • Cytokine
    • T-cell cluster

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