CD8α2 CD11b+ Dendritic Cells Present Exogenous Virus-like Particles to CD8+ T Cells and Subsequently Express CD8α and CD205 Molecules

Abstract

Recombinant porcine parvovirus virus-like particles (PPV-VLPs) are particulate exogenous antigens that induce a strong, specific cytotoxic T lymphocyte (CTL) response in the absence of adjuvant. In the present report, we demonstrate in vivo that dendritic cells (DCs) present PPV-VLPs to CD8+ T cells after intracellular processing. PPV-VLPs are captured by DCs with a high efficacy, which results in the delivery of these exogenous antigens to 50% of the whole spleen DC population. In vivo, a few hours after injection, PPV-VLPs are presented exclusively to CD8+ T cells by CD8α− DCs, whereas 15 hours later they are presented mainly by CD8α+ DCs. After PPV-VLPs processing, a fraction of CD11b+ DCs undergo phenotypic changes, i.e., the up-regulation of CD8α and CD205 and the loss of CD4 molecules on their surface. The failure to detect mRNA coding for CD8α in CD11b+ DCs suggests that CD8α expression by these cells is not due to de novo synthesis. In recombination-activating gene knockout mice (Rag−/−), CD11b+ DCs did not express CD8α and PPV-VLPs presentation by CD8α+ DCs was severely diminished. These results indicate that both CD8α− and CD8α+ DCs play an important role in the induction of CTL responses by exogenous antigens, such as VLP.

Anatomic location defines antigen presentation by dendritic cells to T cells in response to intravenous soluble antigens

“…Martinez del Hoyo et al reported that splenic CD8a -DC differentiate into CD8a + DC in vivo [30], although another recent study presented conflicting results [31]. Moreover, several recent studies indicate that the surface expression level of CD11b on CD8a + and CD8a -DC subsets changes during maturation or after Ag uptake, at least in the spleen [32,33]. In this study, we could not determine whether DC underwent phenotypic change after OVA uptake, because we isolated DC at a single time point after OVA administration.…”

Cutting Edge: Conventional CD8α+ Dendritic Cells Are Preferentially Involved in CTL Priming After Footpad Infection with Herpes Simplex Virus-1

“…Although originally the expression of CD8␣ was used to mark DCs thought to be of lymphoid origin (1,34), it is now clear that this surface Ag is expressed on a variety of quite different DC subsets. We were interested in two particular subsets expressing CD8 that have been implicated in either CTL priming (12,13,35) or antiviral immunity (5,14). The first is the conventional CD8 DC subset identified by Vremec et al (1) and which has recently been shown to be important in cross-presentation of Ag for both CTL priming and tolerance (12,29).…”

“…These DCs have been shown to preferentially cross-present model cell-associated Ags to prime CD8 ϩ T cell responses, consistent with the notion that they play a key role in generating antiviral immunity (12). However, while this subset has been shown to preferentially present class I-restricted Ag derived from nonreplicating virus-like particles (13), there is currently no comparable data involving an infectious live virus. In addition, other DC subsets have been implicated in other aspects of antiviral immunity.…”

Vaccinia virus infection induces dendritic cell maturation but inhibits antigen presentation by MHC class II

“…Indeed, an lymphocytic choriomeningitis virus infection has been shown to change the predominant DC subset from pDC to mDC to divert host immune response away from anti-viral immunity [24]. On the other hand, it was reported that pDC accumulate in the spleen after infection with murine cytomegalovirus [25], and that mDC present exogenous virus-like particles to CD8 T cells and subsequently become CD8 + [26].…”