Journal
BLOOD
Volume 122, Issue 3, Pages 405-412Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-02-483586
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Funding
- Deutsche Forschungsgemeinschaft [Sonderforschungsbereiche SFB 633 (B10), SFB TR36 (A11), DFG Th 806/5-1]
- BCRT/BMBF
- BMBF research network STThera [01GU0802]
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CD8(+) T cells play an essential role in immunity against intracellular pathogens, with cytotoxicity being considered their major effector mechanism. However, we here demonstrate that a major part of central and effector memory CD8(+) T cells expresses CD40L, one key molecule for CD4(+) T-cell-mediated help. CD40L(+) CD8(+) T cells are detectable among human antigen-specific immune responses, including pathogens such as influenza and yellow fever virus. CD40L(+) CD8(+) T cells display potent helper functions in vitro and in vivo, such as activation of antigen-presenting cells, and exhibit a cytokine expression signature similar to CD4(+) T cells and unrelated to cytotoxic CD8(+) T cells. The broad occurrence of CD40L(+) CD8(+) T cells in cellular immunity implicates that helper functions are not only executed by major histocompatibility complex (MHC) class II-restricted CD4(+) helper T cells but are also a common feature of MHC class I-restricted CD8(+) T cell responses. Due to their versatile functional capacities, human CD40L(+) CD8(+) T cells are promising candidate cells for immune therapies, particularly when CD4(+) T-cell help or pathogen-associated molecular pattern signals are limited.
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