Resident Memory T Cells and Their Role within the Liver

Ghilas, Sonia; Valencia-Hernandez, Ana-Maria; Enders, Matthias H.; Heath, William R.; Fernandez‐Ruiz, Daniel

doi:10.3390/ijms21228565

Cited by 9 publications

(8 citation statements)

References 106 publications

(172 reference statements)

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“…[20][21][22][23][24] The induction of CD8 1 T cells, specifically liver-resident memory CD8 1 T (Trm) cells, appears to be critical for long-term protection. 5,13,14,25,26 While the production of aseptic, purified, cryopreserved PfSPZ vaccines has seen significant advances in manufacturing, reducing the dosage or number of doses of PfSPZ would nonetheless significantly reduce the cost of goods.…”

Section: Introductionmentioning

confidence: 99%

Cryopreserved Sporozoites with and without the Glycolipid Adjuvant 7DW8-5 Protect in Prime-and-Trap Malaria Vaccination

Watson

Shears

Matsubara

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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Repeated intravenous (IV) administration of radiation-attenuated sporozoite (RAS) vaccines induces Plasmodium-specific CD8+ liver-resident T (Trm) cells in mice and achieves sterile protection against challenge. Our heterologous “prime-and-trap” vaccine strategy was previously shown to simplify and improve upon RAS vaccination. Prime-and-trap vaccination combines epidermal priming by DNA-encoded circumsporozoite protein (CSP) antigen followed by a single IV dose of freshly dissected RAS (fresh-RAS) to direct and trap activated and expanding CD8+ T cells in the liver. Prime-and-trap vaccination protects mice against wild-type sporozoite (spz) challenge. Assessment of prime-and-trap vaccines in nonhuman primate (NHP) models and/or humans would be greatly enabled if fresh-RAS could be replaced by cryopreserved RAS (cryo-RAS). Here, we investigated if fresh-RAS could be replaced with cryo cryo-RAS for prime-and-trap vaccination in BALB/cj mice. Despite a reduction in spz vaccine liver burden following cryo-RAS administration compared with fresh-RAS, cryo-RAS induced a similar level of Plasmodium yoelii (Py) CSP-specific CD8+ liver Trm cells and completely protected mice against Pyspz challenge 112 days after vaccination. Additionally, when the glycolipid adjuvant 7DW8-5 was coadministered with cryo-RAS, 7DW8-5 permitted the dose of cryo-RAS to be reduced 4-fold while still achieving high rates of sterile protection. In summary, cryo-RAS with and without 7DW8-5 were compatible with prime-and-trap malaria vaccination in a mouse model, which may accelerate the pathway for this vaccine strategy to move to NHPs and humans.

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Section: Introductionmentioning

confidence: 99%

Cryopreserved Sporozoites with and without the Glycolipid Adjuvant 7DW8-5 Protect in Prime-and-Trap Malaria Vaccination

Watson

Shears

Matsubara

et al. 2022

The American Journal of Tropical Medicine and Hygiene

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“…Classification of cells as T EM and T RM cells can be examined further by assessing the mean fluorescence expression of the following markers: CD101, KLRG1, CX3CR1, CXCR6, CD49a, and CD103 (Ghilas, Valencia-Hernandez, Enders, Heath, & Fernandez-Ruiz, 2020;Holz et al, 2020). As shown in the histograms in Figure 6, liver T RM cells show higher expression of CD49a, CXCR6, and CD101 compared with T EM cells, whereas liver T EM cells have higher expression of KLRG1 and CX3CR1 (Fig.…”

Section: Results Evaluationmentioning

confidence: 99%

Using Full‐Spectrum Flow Cytometry to Phenotype Memory T and NKT Cell Subsets with Optimized Tissue‐Specific Preparation Protocols

et al. 2022

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Full-spectrum flow cytometry is now routinely used in many laboratories internationally, and the demand for this technology is rapidly increasing. With capacity to use larger and more complex staining panels, standardized protocols are required for optimal panel design and analysis. Importantly, for ex vivo analysis, tissue preparation methods also need to be optimized to ensure samples are truly representative of tissues in situ. This is particularly relevant given the recent interest in adaptive immune cells that form residency in specific organs. Here we provide optimized protocols for tissue processing and phenotyping of memory T cells and natural killer T (NKT) cell subsets from liver, lung, spleen, and lymph node using full-spectrum flow cytometry. We provide a 21-color antibody panel for identification of different memory subsets, including tissue-resident memory T (T RM ) cells, which are increasingly regarded as important effectors in adaptive immunity. We show that processing procedures can affect outcomes, with liver T RM cells particularly sensitive to heat, such that accurate evaluation requires fast processing at defined temperatures.

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“…A main characteristic of the adaptive immune system is to form a pool of memory T cells, enabling an effective immune response after pathogen re-exposition. The liver displays intrahepatic tissue resident memory (TRM) cells, which require a different cytokine milieu and have diverse phenotypes compared to their counterparts in the blood ( 83 , 84 ). While in mice the non-circulating liver TRM account for 40–60% of the liver-resident T cells, this amount is significantly higher in humans, where it ranges between 60 and 80%.…”

Section: The Liver Adaptive Immune System: the Specific Role Of Lymph...mentioning

confidence: 99%

The liver-resident immune cell repertoire - A boon or a bane during machine perfusion?

Fodor

Salcher²,

Gottschling³

et al. 2022

Front. Immunol.

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The liver has been proposed as an important “immune organ” of the body, as it is critically involved in a variety of specific and unique immune tasks. It contains a huge resident immune cell repertoire, which determines the balance between tolerance and inflammation in the hepatic microenvironment. Liver-resident immune cells, populating the sinusoids and the space of Disse, include professional antigen-presenting cells, myeloid cells, as well as innate and adaptive lymphoid cell populations. Machine perfusion (MP) has emerged as an innovative technology to preserve organs ex vivo while testing for organ quality and function prior to transplantation. As for the liver, hypothermic and normothermic MP techniques have successfully been implemented in clinically routine, especially for the use of marginal donor livers. Although there is evidence that ischemia reperfusion injury-associated inflammation is reduced in machine-perfused livers, little is known whether MP impacts the quantity, activation state and function of the hepatic immune-cell repertoire, and how this affects the inflammatory milieu during MP. At this point, it remains even speculative if liver-resident immune cells primarily exert a pro-inflammatory and hence destructive effect on machine-perfused organs, or in part may be essential to induce liver regeneration and counteract liver damage. This review discusses the role of hepatic immune cell subtypes during inflammatory conditions and ischemia reperfusion injury in the context of liver transplantation. We further highlight the possible impact of MP on the modification of the immune cell repertoire and its potential for future applications and immune modulation of the liver.

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Resident Memory T Cells and Their Role within the Liver

Cited by 9 publications

References 106 publications

Cryopreserved Sporozoites with and without the Glycolipid Adjuvant 7DW8-5 Protect in Prime-and-Trap Malaria Vaccination

Cryopreserved Sporozoites with and without the Glycolipid Adjuvant 7DW8-5 Protect in Prime-and-Trap Malaria Vaccination

Using Full‐Spectrum Flow Cytometry to Phenotype Memory T and NKT Cell Subsets with Optimized Tissue‐Specific Preparation Protocols

The liver-resident immune cell repertoire - A boon or a bane during machine perfusion?

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