Specific, functional effector/memory CD8+ T cells are found in the liver post-vaccination

Dikopoulos, Nektarios; Jomantaitė, Ieva; Schirmbeck, Reinhold; Reimann, Jörg

doi:10.1016/s0168-8278(03)00469-0

Cited by 13 publications

(20 citation statements)

References 38 publications

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“…Alternatively, the liver and the bone marrow are responsible for homeostatic expansion of nonoverlapping memory T cell subsets, or that renewed memory T cells from the liver and bone marrow may be functionally distinct. Reports contrasting the long-held view that the liver is a graveyard for activated T cells have been published (37)(38)(39). CD8 + memory T cells do more than gain entry and survive in the liver, our results show that they actually grow in the liver.…”

Section: Discussioncontrasting

confidence: 55%

Effector Function-Deficient Memory CD8+ T Cells Clonally Expand in the Liver and Give Rise to Peripheral Memory CD8+ T Cells

Lee

Kung

2010

The Journal of Immunology

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Upon adoptive transfer into histocompatible mice, naive CD8+ T cells stimulated ex vivo by TCR+IL-4 turn into long-lived functional memory cells. The liver contains a large number of so formed memory CD8+ T cells, referred to as liver memory T cells (Tlm) in the form of cell clusters. The CD62Llow expression and nonlymphoid tissue distribution of Tlm cells are similar to effector memory (Tem) cells, yet their deficient cytotoxicity and IFN-γ inducibility are unlike Tem cells. Adoptive transfer of admixtures of TCR+IL-4–activated Vβ8+ and Vβ5+ CD8+ T cells into congenic hosts reveals Tlm clusters that are composed of all Vβ5+ or Vβ8+, not mixed Vβ5+/Vβ8+ cells, indicating that Tlm clusters are formed by clonal expansion. Clonally expanded CD8+ T cell clusters are also seen in the liver of Listeria monocytogenes-immune mice. Tlm clusters closely associate with hepatic stellate cells and their formation is IL-15/IL-15R–dependent. CD62Llow TLM cells can home to the liver and secondary lymphoid tissues, remain CD62Llow, or acquire central memory (Tcm)-characteristic CD62Lhi expression. Our findings show the liver as a major site of CD8+ memory T cell growth and that Tlm cells contribute to the pool of peripheral memory cells. These previously unappreciated Tlm characteristics indicate the inadequacy of the current Tem/Tcm classification scheme and help ongoing efforts aimed at establishing a unifying memory T cell development pathway. Lastly, our finding of Tlm clusters suggests caution against interpreting focal lymphocyte infiltration in clinical settings as pathology and not normal physiology.

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Section: Discussioncontrasting

confidence: 55%

Effector Function-Deficient Memory CD8+ T Cells Clonally Expand in the Liver and Give Rise to Peripheral Memory CD8+ T Cells

Lee

Kung

2010

The Journal of Immunology

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“…The regulation of Ag-specific CD8 responses is therefore of major therapeutic interest (41)(42)(43)(44). In summary, we could show that IL-20R2 regulates T cell activation directly and attenuates Ag-specific CD8 responses.…”

Section: Discussionmentioning

confidence: 79%

IL-20 Receptor 2 Signaling Down-Regulates Antigen-Specific T Cell Responses

Wahl

Müller

Leithäuser³

et al. 2009

The Journal of Immunology

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“…Isolation of spleen cells and hepatic nonparenchymal cells has been described. 6,24 Cells were washed twice in phosphate-buffered saline/ 0.3% w/v bovine serum albumin supplemented with 0.1% w/v sodium azide. Nonspecific binding of antibodies to the Fc receptor was blocked by preincubating cells with mAb 2.4G2 (cat.no.01241D; BD Biosciences, Heidelberg, Germany) directed against the Fc␥RIII/II CD16/CD32 (0.5 g mAb/10 6 cells/ 100 L).…”

Section: Methodsmentioning

confidence: 99%

“…Determination of frequencies of CD8 ϩ T cells specifically inducible to interferon ␥ (IFN␥) expression has been previously described. 6,24 Alternatively, cells from spleen or liver freshly isolated from nonimmune or immune mice (but not restimulated in vitro with peptide) were stained with FITC-conjugated ␣-CD8 mAb, PE-conjugated K b /S2 VWLSVIWM tetramer (ProImmune, Oxford, UK; 0.5 g/10 6 cells/100 L), and additional conjugated mAb's (binding markers of interest) for 30 minutes at 4°C. The cells were then washed twice and analyzed using multicolor flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

Novel peptide-based vaccines efficiently prime murine “help”-independent CD8+ T cell responses in the liver

et al. 2004

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Vaccines for the prophylactic and/or therapeutic immunization against hepatotropic pathogens (e.g., hepatitis B and hepatitis C virus) should establish long-lasting, specific antiviral effector/memory CD8 ؉ T cell immunity in the liver. We describe a novel peptide-based vaccine in which antigenic major histocompatibility complex Class I-binding peptides are fused to a cationic (e.g., human immunodeficiency virus tat-derived) domain and complexed to immune-stimulating oligonucleotides. This vaccine formulation efficiently primes liverhoming, Class I-restricted CD8 ؉ effector/memory T cell responses. In different antigen systems, this formulation was more potent in priming liver-homing CD8 ؉ T cell responses than DNA-based vaccines delivering the same epitopes. CD8 ؉ T cell priming was independent of CD4 ؉ T cell "help" but submitted to regulatory control by CD25 ؉ CD4 ؉ T cells. The vaccine efficiently primed memory/effector CD8 ؉ T cells detectable in the liver for more than 3 months after a single injection. With increasing time after priming, the phenotype of these specific memory CD8 ؉ T cells shifted from an effector memory to a central memory type. The vaccine could override T cell tolerance in mice expressing the relevant antigen from a transgene in the liver. The CD8 ؉ T cell immunity in the liver primed by this peptide formulation could be boosted by challenge injections. In conclusion, we describe a simple and potent vaccine formulation that has the potential to generate or reconstitute specific CD8 ؉ T cell immunity to hepatotropic pathogens in the liver. (HEPATOLOGY 2004;40: 300 -309.)

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Specific, functional effector/memory CD8+ T cells are found in the liver post-vaccination

Cited by 13 publications

References 38 publications

Effector Function-Deficient Memory CD8+ T Cells Clonally Expand in the Liver and Give Rise to Peripheral Memory CD8+ T Cells

Effector Function-Deficient Memory CD8+ T Cells Clonally Expand in the Liver and Give Rise to Peripheral Memory CD8+ T Cells

IL-20 Receptor 2 Signaling Down-Regulates Antigen-Specific T Cell Responses

Novel peptide-based vaccines efficiently prime murine “help”-independent CD8+ T cell responses in the liver

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