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

Abstract

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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Figure 1: Gradual decrease in memory CD8+ T cell numbers in MHC class II–deficient versus wild-type mice.
Figure 2: Changes in IL-7Rα expression on CD8+ T cells during the programming and memory phases in wild-type and MHC class II–deficient mice.
Figure 3: Transfer of effector CD8+ T cells demonstrates that CD4+ T cells are required after, but not during, the programming phase for the development of stable CD8 memory.
Figure 4: Effector CD8+ T cells transferred to MHC class II–deficient mice become functionally impaired.
Figure 5: Effector CD8+ T cells transferred to MHC class II–deficient mice are unable to confer protection against bacterial challenge.
Figure 6: Transfer of memory cells demonstrates that CD4+ T cells are required for the maintenance of CD8+ T cell memory.

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Acknowledgements

Supported by the National Institutes of Health (AI19335, AI056809 and CA09537) and the Howard Hughes Medical Institute.

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Correspondence to Michael J Bevan.

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Supplementary information

Supplementary Fig. 1

GP(33-41)-specific CD8+ T cell numbers in the liver and lymph nodes of MHC class II-deficient and wild-type mice following infection. (PDF 22 kb)

Supplementary Fig. 2

Changes in surface phenotype and cytokine production in CD8+ T cells during the effector and memory phases in wild-type and MHC class II-deficient mice. (PDF 60 kb)

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Sun, J., Williams, M. & Bevan, M. CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection. Nat Immunol 5, 927–933 (2004). https://doi.org/10.1038/ni1105

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