Cutting Edge: Intravascular Staining Redefines Lung CD8 T Cell Responses

Anderson, Kristin G.; Sung, Heungsup; Skon, Cara N.; Lefrançois, Leo; Deisinger, Angela; Vezys, Vaiva; Masopust, David

doi:10.4049/jimmunol.1201682

Cited by 275 publications

(321 citation statements)

References 25 publications

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“…However, an intravascular staining approach was recently used to demonstrate that perfusion was far from effective in removing T-cells from the pulmonary vasculature. In fact, up to 97% of the CD8 T-cells thought to be located in the lung interstitium were present in the lung vasculature following a respiratory viral infection [16]. This observation questions the previous conclusions, including our own, and necessitates revisiting the anatomic distribution of lung T-cell responses following different routes of immunisation.…”

Section: Protection Against Pulmonary Tb Is Determined By the Differecontrasting

confidence: 52%

“…The availability of the recently developed technique of intravascular staining helps to discriminate pulmonary intravascular and lung tissue T-cell populations for the first time [16,17], and appreciate their relationship with anti-TB protection. In our previous studies we have reported that, regardless of route of immunisation, a large population of anti-TB T-cells can be isolated from perfused mouse lungs [12,13].…”

Section: Protection Against Pulmonary Tb Is Determined By the Differementioning

confidence: 99%

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Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments

et al. 2015

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Despite the use of bacille Calmette-Guérin (BCG) for almost a century, pulmonary tuberculosis (TB) continues to be a serious global health concern. Therefore, there has been a pressing need for the development of new booster vaccines to enhance existing BCG-induced immunity. Protection following mucosal intranasal immunisation with AdHu5Ag85A is associated with the localisation of antigen-specific T-cells to the lung airway. However, parenteral intramuscular immunisation is unable to provide protection despite the apparent presence of antigen-specific T-cells in the lung interstitium. Recent advances in intravascular staining have allowed us to reassess the previously established T-cell distribution profile and its relationship with the observed differential protection. Respiratory mucosal immunisation empowers T-cells to home to both the lung interstitium and the airway lumen, whereas intramuscular immunisation-activated T-cells are largely trapped within the pulmonary vasculature, unable to populate the lung interstitium and airway. Given the mounting evidence supporting the safety and enhanced efficacy of respiratory mucosal immunisation over the traditional parenteral immunisation route, a greater effort should be made to clinically develop respiratory mucosal-deliverable TB vaccines. @ERSpublications Immunisation route determines TB vaccine efficacy based on whether T-cells can enter restricted lung mucosal sites http://ow.ly/M0shT

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Section: Protection Against Pulmonary Tb Is Determined By the Differecontrasting

confidence: 52%

Section: Protection Against Pulmonary Tb Is Determined By the Differementioning

confidence: 99%

Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments

et al. 2015

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“…Our finding that epidermal T RM also use AhR for maintenance, combined with data showing that T RM can displace DETCs in the skin, suggest that epidermal T cells compete for space within a niche that is influenced at least in part by the availability of AhR ligands. Further work will be needed to determine the signals involved in the maintenance of T RM in other tissues such as the gut and lung, which also persist in defined microenvironments (27,28). In conclusion, our data demonstrate the dynamic nature of T RM migration and persistence in skin and suggest a basis for the regulation of T-cell populations within an epidermal niche.…”

Section: Discussionmentioning

confidence: 81%

Persistence of skin-resident memory T cells within an epidermal niche

Zaid

Mackay

Rahimpour

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

262

310

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Barrier tissues such as the skin contain various populations of immune cells that contribute to protection from infections. These include recently identified tissue-resident memory T cells (T RM ). In the skin, these memory CD8 + T cells reside in the epidermis after being recruited to this site by infection or inflammation. In this study, we demonstrate prolonged persistence of epidermal T RM preferentially at the site of prior infection despite sustained migration. Computational simulation of T RM migration within the skin over long periods revealed that the slow rate of random migration effectively constrains these memory cells within the region of skin in which they form. Notably, formation of T RM involved a concomitant local reduction in dendritic epidermal γδ T-cell numbers in the epidermis, indicating that these populations persist in mutual exclusion and may compete for local survival signals. Accordingly, we show that expression of the aryl hydrocarbon receptor, a transcription factor important for dendritic epidermal γδ T-cell maintenance in skin, also contributes to the persistence of skin T RM . Together, these data suggest that skin tissue-resident memory T cells persist within a tightly regulated epidermal T-cell niche. T he skin is a complex organ that acts as a primary barrier between the body and the environment. Multiple leukocyte subsets reside within the main compartments of the skin, the dermis and the epidermis, as well as the hair follicles that are contiguous with the epidermis. Populations of macrophages, dendritic cells, mast cells, γδ T cells and αβ T cells are present in the dermis, and Langerhans cells (LCs) and dendritic epidermal γδ T cells (DETCs) lie in a strategic network in the epidermis (1). We recently described a population of memory CD8 + T cells that enter the epidermis and hair follicles during infection or inflammation and become long-lived populations of tissue-resident memory T cells (T RM ) (2-5). These memory T cells are sequestered in this site and are distinct from circulating effector memory (T EM ) and central memory (T CM ) populations (3, 6). Memory CD8 + T cells in the epidermis display a dendritic morphology and move at a slower velocity than T cells within the dermis. These memory T cells are sequestered in the skin epithelial layer and do not recirculate to other tissues. In contrast, memory CD4 + T cells are found within the dermis and at least a proportion of these cells are capable of recirculating around the body (3, 7).In this study, we sought to further examine the mechanisms of T RM persistence within the skin. We reveal that skin T RM persist at the site of their formation and despite displaying a sustained mode of random migration, the slow rate of this movement locally constrains these memory cells. Examination of other cells in this environment showed that although epidermal T RM regularly interact with LC, these interactions were not required for persistence. In contrast, skin tissue-resident memory T cells replaced DETCs in the epidermis, seem...

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“…It now appears that much of that recirculation can be attributed to blood contamination of the permissive organs (35). Residency is far more widespread than previously envisaged, and its basis is inherent to the T RM cells rather than the tissue in which they lodge (27,36,37).…”

Section: T Rm Cell Lodgement In Diverse Lymphoid and Nonlymphoid Tissuesmentioning

confidence: 90%

Tissue-Resident Memory T Cells and Fixed Immune Surveillance in Nonlymphoid Organs

Carbone

2015

The Journal of Immunology

116

110

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T cell immunity is often defined in terms of memory lymphocytes that use the blood to access a range of organs. T cells are involved in two patterns of recirculation. In one, the cells shuttle back and forth between blood and secondary lymphoid organs, whereas in the second, memory cells recirculate between blood and nonlymphoid tissues. The latter is a means by which blood T cells control peripheral infection. It is now clear that there exists a distinct memory T cell subset that is absent from blood but found within nonlymphoid tissues. These nonrecirculating tissue-resident memory T (TRM) cells develop within peripheral compartments and never spread beyond their point of lodgement. This review examines fixed immune surveillance by TRM cells, highlighting features that make them potent controllers of infection in nonlymphoid tissues. These features provide clues about TRM cell specialization, such as their ability to deal with sequestered, persisting infections confined to peripheral compartments.

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Cutting Edge: Intravascular Staining Redefines Lung CD8 T Cell Responses

Cited by 275 publications

References 25 publications

Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments

Mucosal immunity and novel tuberculosis vaccine strategies: route of immunisation-determined T-cell homing to restricted lung mucosal compartments

Persistence of skin-resident memory T cells within an epidermal niche

Tissue-Resident Memory T Cells and Fixed Immune Surveillance in Nonlymphoid Organs

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