Minimal activation of memory CD8+ T cell by tissue-derived dendritic cells favors the stimulation of naive CD8+ T cells

Abstract

Of the many dendritic cell (DC) subsets, DCs expressing the monomorphic coreceptor CD8 alpha-chain (CD8alpha) are localized permanently in lymphoid organs, whereas 'tissue-derived DCs' remain in nonlymphoid tissues until they 'capture' antigen and then move to local lymph nodes. Here we show that after lung infection, both naive and memory CD8+ 'killer' T cells responded to influenza virus antigens presented by lymph node-resident CD8alpha+ DCs, but only naive cells responded to antigens presented by lung-derived DCs. This difference provides a mechanism for priming naive T cell responses in conditions in which robust memory predominates. Our findings have implications for immunity to pathogens that can mutate their T cell epitopes, such as influenza virus and human immunodeficiency virus, and challenge the long-held view that memory T cells have less-stringent requirements for activation than naive T cells have.

Origin and functional specializations of DC subsets in the lung

“…Legge demonstrated that these CD11b 1 inflammatory DC indeed boost CD8 1 effector activity in the lung [49]. Other studies have shown that CD103 1 CD11b À lung cDC cannot present antigen to virus-specific effector CD8 1 T lymphocytes [47]. Secondly, CD11b 1 DC can display direct antiviral potential through the release of TNF and production of iNOS-derived NO, as shown during Listera monocytogenes infection [50], and thus might also contribute to influenza pathogenesis and systemic disease.…”

“…The CD11b À migratory DC stimulated CD4 1 and CD8 1 lymphocyte responses, whereas CD11b 1 DC were very poorly immunogenic. A population of CD8a 1 CD11b À non-migratory cDC also acquired antigen from migratory CD11b À and CD11b 1 cells and crosspresented viral antigen to CD8 1 T cells [2,47]. Depletion of lung CD11b À cDC in langerin-diphtheria toxin receptor Tg mice (langerin-DTR) and of resident CD8a 1 cDC using CD11c-DTR Tg mice severely hampered the induction of virus-specific tetramer-positive CD8 1 T cells and delayed viral clearance from the lung [2].…”

Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination

“…18,[34][35][36] In vitro programming was accomplished in the following manner. In all experiments, day 7 pmel T EM cells were frozen.…”

Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses

“…Within the draining LN, DC subsets, primarily CD103 + DCs that migrated from the infected respiratory tract, as well as LN resident CD8α + DCs, present antigen to CD8 T cells (14)(15)(16)(17)(18). These DCs can acquire IAV antigens by at least three distinct mechanisms: (i) through direct infection, (ii) through phagocytosis of necrotic or apoptotic IAV-infected epithelial cells, or (iii) through membrane exchange with infected cells and transfer of peptide-loaded MHC I (1)(2)(3)(4)(5)(6)(19)(20)(21)(22).…”