CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes

Edith M. Janssen, Edward E. Lemmens, Tom Wolfe, Urs Christen, Matthias G. von Herrath and Stephen P. Schoenberger ()
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Tom Wolfe: La Jolla Institute for Allergy and Immunology
Urs Christen: La Jolla Institute for Allergy and Immunology
Matthias G. von Herrath: La Jolla Institute for Allergy and Immunology
Stephen P. Schoenberger: La Jolla Institute for Allergy and Immunology

Nature, 2003, vol. 421, issue 6925, 852-856

Abstract: Abstract A long-standing paradox in cellular immunology concerns the conditional requirement for CD4+ T-helper (TH) cells in the priming of cytotoxic CD8+ T lymphocyte (CTL) responses in vivo. Whereas CTL responses against certain viruses can be primed in the absence of CD4+ T cells, others, such as those mediated through ‘cross-priming’ by host antigen-presenting cells, are dependent on TH cells1,2,3,4. A clearer understanding of the contribution of TH cells to CTL development has been hampered by the fact that most TH-independent responses have been demonstrated ex vivo as primary cytotoxic effectors, whereas TH-dependent responses generally require secondary in vitro re-stimulation for their detection. Here, we have monitored the primary and secondary responses of TH-dependent and TH-independent CTLs and find in both cases that CD4+ T cells are dispensable for primary expansion of CD8+ T cells and their differentiation into cytotoxic effectors. However, secondary CTL expansion (that is, a secondary response upon re-encounter with antigen) is wholly dependent on the presence of TH cells during, but not after, priming. Our results demonstrate that T-cell help is ‘programmed’ into CD8+ T cells during priming, conferring on these cells a hallmark of immune response memory: the capacity for functional expansion on re-encounter with antigen.

Date: 2003
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DOI: 10.1038/nature01441

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