Short-term antigen presentation and single clonal burst limit the magnitude of the CD8+ T cell responses to malaria liver stages

It has been reported that MHC class I-restricted Ag presentation persists for only a short period following infection with certain pathogens, declining in parallel with the emergence of specific CTL activity. We have examined this issue in the case of murine infection with HSV-1. We found that the period of Ag presentation capable of priming naive CD8+ T cells is comparatively prolonged, persisting for at least 7 days after infection, and continuing despite the appearance of localized CTL activity. Ag presentation was abbreviated to 3 or 4 days postinfection by surgical excision of the inoculation site early after infection. This intervention attenuated the size of the primary CTL response, implying that prolonged presentation is necessary to drive maximal CTL expansion. Combined, these data show that, in some types of infection, CTL priming can extend well beyond the first 24–48 h after primary inoculation.

Section: Discussionsupporting

confidence: 54%

supporting

confidence: 69%

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Cutting Edge: Prolonged Antigen Presentation after Herpes Simplex Virus-1 Skin Infection

Stock

Mueller

Lint

et al. 2004

“…This is difficult to assess because activated APCs drive the development of CD8 T cell cytolytic activity, which, in turn, would lead to the clearance of Ag. Indeed, recent findings have shown that CD8 T cells that are activated in response to a pathogen such as Listeria monocytogenes or malaria quickly kill APCs (28,29). Such removal of APCs may be an important part of the strategy by which the immune system prevents deletion of primed effector and memory cells.…”

Section: Discussionmentioning

confidence: 99%

Deletion of Naive CD8 T Cells Requires Persistent Antigen and Is Not Programmed by an Initial Signal from the Tolerogenic APC

Redmond

Hernandez

Sherman

2003

Activation of naive CD8 T cells in vivo requires the recognition of cognate peptide-MHC complexes on APCs. Depending upon the activation status of the APC, such recognition will promote either a vigorous immune response or T cell tolerance and deletion. Recent studies suggest that the initial signals provided by APCs are sufficient to program the proliferation of naive CD8 T cells and their differentiation into effector cells. In this study, we sought to determine whether an initial encounter with tolerogenic APCs was sufficient to program deletion of naive CD8 T cells. Surprisingly, we find that regardless of whether naive CD8 T cells were stimulated by activated or quiescent APCs, transfer of the activated T cells into an Ag-free host was sufficient to ensure survival. Thus, although the extent of clonal expansion and development of effector function is determined by the activation status of the stimulatory APC, peripheral clonal deletion requires persistent Ag and is not determined by the initial stimulatory event.

“…For CD8 + T cells, it has been shown that antigenic signals beyond an initial period are not required for proliferation (4)(5)(6)(7)(8)(9)(10), thus supporting the notion of early programming of CD8 + T cell expansion (11,12). However, there is also data that CD8 + T cell expansion is correlated with the continued duration of TCR stimulation in the context of both infections and sterile vaccinations (13)(14)(15)(16)(17)(18)(19)(20)(21).…”

Section: T Cell Receptor-mediated Recognition Of Antigenic Peptidesmentioning

confidence: 92%

Differential Kinetics of Antigen Dependency of CD4+ and CD8+ T Cells

Rabenstein

Ellwart

et al. 2014

Ag recognition via the TCR is necessary for the expansion of specific T cells that then contribute to adaptive immunity as effector and memory cells. Because CD4+ and CD8+ T cells differ in terms of their priming APCs and MHC ligands we compared their requirements of Ag persistence during their expansion phase side by side. Proliferation and effector differentiation of TCR transgenic and polyclonal mouse T cells were thus analyzed after transient and continuous TCR signals. Following equally strong stimulation, CD4+ T cell proliferation depended on prolonged Ag presence, whereas CD8+ T cells were able to divide and differentiate into effector cells despite discontinued Ag presentation. CD4+ T cell proliferation was neither affected by Th lineage or memory differentiation nor blocked by coinhibitory signals or missing inflammatory stimuli. Continued CD8+ T cell proliferation was truly independent of self-peptide/MHC-derived signals. The subset divergence was also illustrated by surprisingly broad transcriptional differences supporting a stronger propensity of CD8+ T cells to programmed expansion. These T cell data indicate an intrinsic difference between CD4+ and CD8+ T cells regarding the processing of TCR signals for proliferation. We also found that the presentation of a MHC class II–restricted peptide is more efficiently prolonged by dendritic cell activation in vivo than a class I bound one. In summary, our data demonstrate that CD4+ T cells require continuous stimulation for clonal expansion, whereas CD8+ T cells can divide following a much shorter TCR signal.