The emerging role of resident memory T cells in protective immunity and inflammatory disease

Park, Chang Ook; Kupper, Thomas S.

doi:10.1038/nm.3883

Cited by 451 publications

(467 citation statements)

References 124 publications

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“…Although lymphocytes are best characterized in the blood, lymphatic fluid, and lymphoid organs, interest in tissue-resident lymphocytes is currently emerging (33)(34)(35)(36)(37). Different lymphocyte populations have now been described in several nonlymphoid organs, where they can influence the local molecular milieu and modulate other resident cells (38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Myocardial aging as a T-cell–mediated phenomenon

Ramos

Berg²,

Silva

et al. 2017

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

142

117

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In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissueresident leukocytes and with an accumulation of activated CD4 + Foxp3 − (forkhead box P3) IFN-γ + T cells in the heart-draining lymph nodes. A comprehensive characterization of different aged immune-deficient mouse strains revealed that T cells significantly contribute to age-related myocardial inflammation and functional decline. Upon adoptive cell transfer, the T cells isolated from the mediastinal lymph node (med-LN) of aged animals exhibited increased cardiotropism, compared with cells purified from young donors or from other irrelevant sites. Nevertheless, these cells caused rather mild effects on cardiac functionality, indicating that myocardial aging might stem from a combination of intrinsic and extrinsic (immunological) factors. Taken together, the data herein presented indicate that heart-directed immune responses may spontaneously arise in the elderly, even in the absence of a clear tissue damage or concomitant infection. These observations might shed new light on the emerging role of T cells in myocardial diseases, which primarily affect the elderly population.T he myocardial cellular composition has been revisited in recent years, and leukocyte subsets residing in the healthy heart have been described (1-10). Cardiac-resident macrophages exhibiting an M2-like gene expression profile were found to be distributed in close association with the coronary vascular bed (3), and niches for dendritic cells (CD11c + MHC-II high CD80/86 low ) were found near the cardiac valves of the intact heart (1). It was also demonstrated that cardiac-resident MHCII + cells process and present myosin heavy chain-alpha-derived peptides under steady-state conditions (11, 12) and prime T cells ex vivo (1). However, whether lymphocytes can seed the intact myocardium and whether T-cell priming with myocardial antigens can occur in the absence of an infection or autoimmune myocarditis remain elusive.More recently, accumulating evidence indicated that noninfectious myocardial diseases are modulated by T cells. During the last couple of years, our group demonstrated that ischemic, sterile myocardial injuries can elicit lymphocyte activation directed against cardiac antigens (13-16). Our previous data, showing for the first time that CD4 + T cells reactive to cardiac components can foster the healing process that takes place after myocardial infarction, were corroborated by several other reports (13,15,(17)(18)(19)(20). However, these autoreactive T cells can also b...

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Section: Discussionmentioning

confidence: 99%

Myocardial aging as a T-cell–mediated phenomenon

Ramos

Berg²,

Silva

et al. 2017

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

142

117

View full text Add to dashboard Cite

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“…Analyses of cell surface markers CD69 and CD27 suggested significantly higher levels of Vα2.3 + Vβ22 + T-cells to be activated, and also to be differentiated to a higher degree compared to their Vα2.3 − Vβ22 − CD4 + T-cells counterparts, likely reflecting antigenic stimulation. Alternatively, the high CD69 expression reflects a tissue-resident memory T-cell phenotype, suggested to be of importance for human tissue-specific immune and inflammatory diseases [25].…”

Section: Discussionmentioning

confidence: 99%

T-cell receptor–HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis

et al. 2015

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In pulmonary sarcoidosis, CD4+ T-cells expressing T-cell receptor Vα2.3 accumulate in the lungs of HLA-DRB1*03 + patients. To investigate T-cell receptor-HLA-DRB1*03 interactions underlying recognition of hitherto unknown antigens, we performed detailed analyses of T-cell receptor expression on bronchoalveolar lavage fluid CD4 + T-cells from sarcoidosis patients. Pulmonary sarcoidosis patients (n=43) underwent bronchoscopy with bronchoalveolar lavage. T-cell receptor α and β chains of CD4 + T-cells were analysed by flow cytometry, DNA-sequenced, and threedimensional molecular models of T-cell receptor-HLA-DRB1*03 complexes generated.Simultaneous expression of Vα2.3 with the Vβ22 chain was identified in the lungs of all HLA-DRB1*03 + patients. Accumulated Vα2.3/Vβ22-expressing T-cells were highly clonal, with identical or near-identical Vα2.3 chain sequences and inter-patient similarities in Vβ22 chain amino acid distribution. Molecular modelling revealed specific T-cell receptor-HLA-DRB1*03-peptide interactions, with a previously identified, sarcoidosis-associated vimentin peptide, (Vim)429-443 DSLPLVDTHSKRTLL, matching both the HLA peptide-binding cleft and distinct T-cell receptor features perfectly.We demonstrate, for the first time, the accumulation of large clonal populations of specific Vα2.3/Vβ22 T-cell receptor-expressing CD4 + T-cells in the lungs of HLA-DRB1*03 + sarcoidosis patients. Several distinct contact points between Vα2.3/Vβ22 receptors and HLA-DRB1*03 molecules suggest presentation of prototypic vimentin-derived peptides. @ERSpublications Clonal CD4 + lung T-cells associating with HLA-DRB1*03 molecules indicate specific antigens in pulmonary sarcoidosis

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“…The persistence of T cells in peripheral tissues after resolution of inflammation is a hallmark of resident memory T cells (T RM cells) (11). T RM cells are generated by immune challenges in peripheral tissues, provide rapid responses to rechallenge, and persist in the absence of antigen (12). Studies using mouse infection models have demonstrated that immune challenges in skin, whether they are infectious or hapten driven, lead to colonization of the entire skin surface with antigen-specific T RM (13,14).…”

Section: Putative Pathogenic T Cell Clones Utilize a Skewed Tcr Vα Rementioning

confidence: 99%

Clinically resolved psoriatic lesions contain psoriasis-specific IL-17–producing αβ T cell clones

Matos

O’Malley

Lowry

et al. 2017

Journal of Clinical Investigation

225

197

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Kit (QIAGEN) per the manufacturer's instructions, with overnight tissue digestion. This method generated 155-3730 ng DNA per sample.HTS analyses: immunosequencing. For each sample, DNA was extracted from skin biopsies, then TCRβ CDR3, TCRγ CDR3, TCRα CDR3, and TCRδ CDR3 regions were amplified and sequenced using immunoSEQ (Adaptive Biotechnologies). Bias-controlled V and J gene matitis, allergic contact dermatitis, and pityriasis lichenoides were obtained with IRB approval from the Pathology Specimen Locator Core at Brigham and Women's Hospital.DNA isolation from skin. DNA was isolated from frozen, OCTembedded skin samples. 30 Cryosections of 10-μm thickness were cut, and DNA extraction was carried out using the QIAamp DNA Mini

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The emerging role of resident memory T cells in protective immunity and inflammatory disease

Cited by 451 publications

References 124 publications

Myocardial aging as a T-cell–mediated phenomenon

Myocardial aging as a T-cell–mediated phenomenon

T-cell receptor–HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis

Clinically resolved psoriatic lesions contain psoriasis-specific IL-17–producing αβ T cell clones

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