Switching from a restricted to an effective CD4 T cell response by activating CD8+ murine dendritic cells with a Toll-like receptor 9 ligand

Abstract

Freshly isolated quiescent splenic dendritic cell (DC) subtypes differ in their capacity to activate naive CD4 T cells in culture. The CD8 + DC showed a reduced capacity to stimulate T cell proliferation compared to either of the CD8 -DC subsets, regardless of antigen and DC dose. In contrast to CD8 -DC, the quiescent CD8 + DC did not induce IFN-c production from CD4 T cells. The difference between the DC subtypes appeared to be at the level of initial surface molecule interactions, but could not be attributed to differences in expression of MHC class II or B7 family molecules, or to the expression of Fas ligand on DC. However, when activated by inclusion of the Toll-like receptor 9 ligand CpG in culture, CD8 + DC became potent stimulators of both CD4 T cell proliferation and IFN-c production. In contrast, similar activation of CD8 -DC produced a more modest increase in capacity to stimulate CD4 T cell proliferation and no increase in capacity to stimulate IFN-c production. The difference between a quiescent and an activated state is therefore more extreme for CD8 + than for CD8 -DC. The especially tight regulation of the activity of CD8 + DC may be essential for the maintenance of self tolerance.

Rabbit Polyclonal Mouse Antithymocyte Globulin Administration Alters Dendritic Cell Profile and Function in NOD Mice to Suppress Diabetogenic Responses

“…Finally, we noted higher proliferation in T cell cultures stimulated with mATG treated DC (CD8 − predominant) or purified CD8 − DC from naïve NOD. These findings are consistent with reports by the Shortman group (32,33) which noted a reduced capacity of quiescent splenic CD8 + DC versus CD8 − DC to stimulate T cell proliferation.…”

“…The authors of those studies suggested that the increase in PLN CD8 − DCs represented an increased migration from the pancreas (16, 17). However, ascribing tolerogenic function solely to one individual DC subtype is still controversial, since some groups have reported that CD8 + DC can also induce tolerance to tissue-associated antigens (32,33). …”

Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation

“…It is possible that CD141 + DDCs may exert antimicrobial or antiviral immunity when encountering viral/microbial products or under specific environmental conditions. TLR9 ligation was reported to reverse the regulatory function of CD8 + DCs and promote T cell immunity in mice (Rizzitelli et al, 2005). Thus, our study does not exclude the possibility that CD141 + DDCs may be stimulatory in the context of viral/microbial infection and inflammatory skin pathology.…”

Histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in SKG mice

“…These results suggested that TSA mainly affected the CD8α + conventional dendritic cell population in vivo . CD8α + conventional dendritic cells are considered a more developed or activated form of CD8α - conventional dendritic cells, because CD8α + conventional dendritic cells have been shown to more potently induce CD4 + T cell proliferation and interferon-γ production compared with similarly activated CD8α - conventional dendritic cells [47-49]. Recently, CD8α + conventional dendritic cells have been shown to produce IL-12p70 and induce antigen-specific Th17 and Th1 cells, resulting in the acceleration of collagen-induced arthritis [50].…”