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The Journal of Immunology, 2006, 176: 3028-3036.
Copyright © 2006 by The American Association of Immunologists

Precursor Frequency, Nonlinear Proliferation, and Functional Maturation of Virus-Specific CD4+ T Cells1

Jason K. Whitmire, Nicola Benning and J. Lindsay Whitton2

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037

The early events regulating antiviral CD4 responses were tracked using an adoptive transfer model. CD4+ T cell expansion was nonlinear, with a lengthy lag phase followed by 2 days of explosive proliferation. A small number of naive Ag-specific CD4+ T cells were found in nonlymphoid tissues and, in the 8 days following infection, the number of activated cells increased in all tissues analyzed, and their effector functions matured. Finally, we show that a naive mouse contains ~100 naive CD4+ precursor cells specific for a single epitope, a precursor frequency of ~10–5, similar to that of naive CD8+ T cells, indicating that the ~50-fold difference in size of the two responses to virus infection is determined by something other than the number of precursor cells.




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