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Nat Immunol. 2004 Sep;5(9):927-33. Epub 2004 Aug 8.

CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection.

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Department of Immunology and the Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.


Immunization in the absence of CD4(+) T cell help results in defective CD8(+) T cell memory, deficient recall responses and diminished protective immunity. Here we investigated at what stage during the immune response to pathogen CD4(+) T cells are essential in the promotion of functional CD8(+) T cell memory. Memory CD8(+) T cell numbers decreased gradually in the absence of CD4(+) T cells despite the presence of similar numbers of memory cell precursors at the peak of the effector phase. Adoptive transfer of effector or memory CD8(+) T cells into wild-type or CD4(+) T cell-deficient mice demonstrated that the presence of CD4(+) T cells was important only after, not during, the early CD8(+) T cell programming phase. In the absence of CD4(+) T cells, memory CD8(+) T cells became functionally impaired and decreased in quantity over time. We conclude that in the context of an acute infection, CD4(+) T cells are required only during the maintenance phase of long-lived memory CD8(+) T cells.

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