Dynamic programming of CD8+ T lymphocyte responses

Stipdonk, Marianne J.B. van; Hardenberg, Gijs; Bijker, Martijn S.; Lemmens, Edward E.; Droin, Nathalie; Green, Douglas R.; Schoenberger, Stephen P.

doi:10.1038/ni912

Cited by 350 publications

(336 citation statements)

References 25 publications

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“…This homing pattern correlated with down modulation of CD62L and CCR7 and stable expression of CD44 and CD49d [50]. In vivo and in vitro studies with CD8 + T cells showed that total signal strength determines functional outcome of differentiation and acquisition of "fitness" [42,[52][53][54]. In line with this, we suggest that T cells that have been triggered multiple times via strong TCR signaling plus costimulatory molecules like CD27 favor differentiation into "fit" effector [20] and memory T cells that ultimately no longer express CD27.…”

Section: Discussionmentioning

confidence: 85%

Properties of murine CD8+CD27- T cells

et al. 2005

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Section: Discussionmentioning

confidence: 85%

Properties of murine CD8+CD27- T cells

et al. 2005

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“…In particular, the cellular environment and the initial priming of naïve CD8 + T cells dictate the efficacy of recall responses, and therefore impact vaccine efficacy 7, 8, 9, 10. Analysis of the early events of IAV‐specific CD8 + T‐cell responses has been limited, in part because numbers of virus‐specific CD8 + T cells remain low during the initial stages following antigen encounter.…”

Section: Introductionmentioning

confidence: 99%

Potential killers exposed: tracking endogenous influenza‐specific CD8⁺ T cells

et al. 2018

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Current influenza A virus (IAV) vaccines stimulate antibody responses that are directed against variable regions of the virus, and are therefore ineffective against divergent strains. As CD8+ T cells target the highly conserved, internal IAV proteins, they have the potential to increase heterosubtypic immunity. Early T‐cell priming events influence lasting memory, which is required for long‐term protection. However, the early responding, IAV‐specific cells are difficult to monitor because of their low frequencies. Here, we tracked the dissemination of endogenous IAV‐specific CD8+ T cells during the initial phases of the immune response following IAV infection. We exposed a significant population of recently activated, CD25+CD43+ IAV‐specific T cells that were not detected by tetramer staining. By tracking this population, we found that initial T‐cell priming occurred in the mediastinal lymph nodes, which gave rise to the most expansive IAV‐specific CD8+ T‐cell population. Subsequently, IAV‐specific CD8+ T cells dispersed to the bronchoalveolar lavage and blood, followed by spleen and liver, and finally to the lung. These data provide important insight into the priming and tissue dispersion of an endogenous CD8+ T‐cell response. Importantly, the CD25+CD43+ phenotype identifies an inclusive population of early responding CD8+ T cells, which may provide insight into TCR repertoire selection and expansion. A better understanding of this response is critical for designing improved vaccines that target CD8+ T cells.

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“…Whether this difference was due to in vivo versus in vitro stimulation or the nature of the stimulus was not clear. Within the first 20 h of stimulation, T cells receive the signals they need to undergo a pre-programmed expansion phase that appears to be independent of further T cell activation [33][34][35][36][37]. Recent evidence also suggests that CD8 T cells kill antigen-presenting DC during the first few days of the response [38].…”

Section: Introductionmentioning

confidence: 99%

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

Dawicki

Watts

2004

Eur J Immunol

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4-1BBL -/-mice have a defect in recall CD8 + T cell responses to viruses, whereas CD4 + T cell responses to virus are unimpaired in these mice. In contrast, both CD4 + and CD8 + T cells respond to 4-1BB ligand (4-1BBL) in vitro. To clarify the role of 4-1BB/4-1BBL in CD4 + versus CD8 + T cell responses in vivo, we compared CD4 (OT-II) and CD8 (OT-I) TCR transgenic T cells responding to the same antigen in an in vivo adoptive transfer model in 4-1BBL +/+ versus 4-1BBL -/-mice. During primary and secondary responses, expression of 4-1BB on in vivo-activated TCR transgenic T cells was earlier and more transient than previously observed in vitro, correlating with expression of the early activation antigen CD69 and preceding the transition to the CD44 hi state. Although 4-1BB is expressed early in the primary response, there was no effect of 4-1BBL deficiency on initial CD8 T cell expansion and only a minor effect on initial CD4 T cell expansion. The major effect of 4-1BB/4-1BBL interaction is on the T cell recall response. This is due to effects of 4-1BBL on maintenance of T cell numbers at the end of the primary response with additional effects of 4-1BBL on secondary expansion of T cells.

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Dynamic programming of CD8+ T lymphocyte responses

Cited by 350 publications

References 25 publications

Properties of murine CD8+CD27- T cells

Properties of murine CD8+CD27- T cells

Potential killers exposed: tracking endogenous influenza‐specific CD8⁺ T cells

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

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Dynamic programming of CD8+ T lymphocyte responses

Cited by 350 publications

References 25 publications

Properties of murine CD8+CD27- T cells

Properties of murine CD8+CD27- T cells

Potential killers exposed: tracking endogenous influenza‐specific CD8+ T cells

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

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Potential killers exposed: tracking endogenous influenza‐specific CD8⁺ T cells