Activation of CD4
            <sup>+</sup>
            T Lymphocytes Improves Wound Healing and Survival After Experimental Myocardial Infarction in Mice

Hofmann, Ulrich; Beyersdorf, Niklas; Weirather, Johannes; Podolskaya, A. A.; Bauersachs, Johann; Ertl, G.; Kerkau, Thomas; Frantz, Stefan

doi:10.1161/circulationaha.111.044164

Cited by 410 publications

(405 citation statements)

References 33 publications

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“…During the last couple of years, our group demonstrated that ischemic, sterile myocardial injuries can elicit lymphocyte activation directed against cardiac antigens (13)(14)(15)(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).…”

supporting

confidence: 73%

“…The mice were kept under light anesthesia with isoflurane [1.5% (vol/vol)], and short-axis two-dimensional echocardiographic images were acquired at the midpapillary and apical levels of the left ventricle (LV). End-diastolic and end-systolic diameters were measured from transversal M-mode tracings, according to standard protocols that were previously established in our laboratory (13,15). Only animals with a basal heart rate of >500 beats per minute (bpm) were included in the analysis.…”

Section: Methodsmentioning

confidence: 99%

“…A cell suspension of whole-heart samples was obtained after collagenase type-II digestion (1,000 IU/mL, 37°C, 30 min) and then ground in Hanks' balanced salt solution containing 1% (wt/vol) BSA (BSS/BSA) using a 40-μM cell strainer, according to previous descriptions (3,7,13,15). Lymph node samples were ground and prepared in BSS/BSA [5% (vol/vol) FCS].…”

Section: Methodsmentioning

confidence: 99%

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Myocardial aging as a T-cell–mediated phenomenon

Ramos

Berg²,

Silva

et al. 2017

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

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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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supporting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Myocardial aging as a T-cell–mediated phenomenon

Ramos

Berg²,

Silva

et al. 2017

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

Self Cite

142

117

View full text Add to dashboard Cite

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“…T lymphocytes have also been studied in wound healing, albeit less extensively. T-cell depletion studies in models of wound healing have produced contradictory results depending on the depletion strategies, species, and mode of injury (64)(65)(66)(67).…”

Section: Discussionmentioning

confidence: 99%

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Ghasemlou

Chiu

Julien

et al. 2015

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

152

142

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Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund's adjuvant (CFA) as a model of adjuvant-and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G + CD11b + neutrophils and T-cell receptor (TCR) β + T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b + Ly6G − myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2 + Ly6C hi ) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b + Ly6G − myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation.pain | inflammation | cytokines | monocytes | macrophages

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“…4 In contrast, Hofmann et al reported that CD4 + T cells were activated and facilitated wound healing of the injured myocardium after MI. 5 They also demonstrated by using OT-II mice (C57BL/6-Tg(TcraTcrb)425Cbn/Crl) that T cell receptor (TCR) signaling is important to activate CD4 + T cells after MI. Consequently, eart failure is the major cause of death after myocardial infarction (MI).…”

mentioning

confidence: 99%