Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 8, Pages 3312-3317Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1018525108
Keywords
cytokine; T-cell cluster
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Funding
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- US Civilian Research and Development Foundation [RUX1-2710-MO-06]
- Russian Foundation for Basic Research [08-01-00141a]
- Russian Academy of Sciences Basic Research for Medicine
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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 similar to-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-alpha receptor, cytotoxic T-lymphocyte antigen-4, IL-2, or IFN-gamma. 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.
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