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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 approximately 100 naive CD4+ precursor cells specific for a single epitope, a precursor frequency of approximately 10(-5), similar to that of naive CD8+ T cells, indicating that the approximately 50-fold difference in size of the two responses to virus infection is determined by something other than the number of precursor cells.

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