RESUMO
Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single-cell RNA and TCR sequencing on recipient-derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with rejection and compare them with T cells obtained from the same patients after treatment of rejection with high-dose systemic glucocorticoids. At the time of rejection, we found an oligoclonal expansion of cytotoxic CD8+ T cells that all persisted as tissue resident memory T cells after successful treatment. Persisting CD8+ allograft-resident T cells have reduced gene expression for cytotoxic mediators after therapy with glucocorticoids but accumulate around airways. This clonal expansion is discordant with circulating T cell clonal expansion at the time of rejection, suggesting in situ expansion. We thus highlight the accumulation of cytotoxic, recipient-derived tissue resident memory T cells within the lung allograft that persist despite the administration of high-dose systemic glucocorticoids. The long-term clinical consequences of this persistence have yet to be characterized.
Assuntos
Glucocorticoides , Transplante de Pulmão , Linfócitos T CD8-Positivos/metabolismo , Glucocorticoides/metabolismo , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Células T de MemóriaRESUMO
The histologic changes occurring in severe/therapy-resistant asthma (SA) as defined by the European Respiratory Society/American Thoracic Society guidelines, particularly at the level of the distal airways are unknown. This study describes the clinical, radiologic, and histologic characteristics of 29 SA patients who underwent video-assisted thoracoscopic surgery lung biopsy. Pathologic observations were correlated with clinical features, especially the presence of autoimmune disease (AID) (15/29, 51.7%). Ten biopsies (10/29, 34.5%) showed only small airway manifestations of asthma, whereas in 19 (65.5%) asthmatic granulomatosis, manifested by asthmatic bronchiolitis supplemented by an alveolar septal mononuclear infiltrates with non-necrotizing granulomas, was present. SA patients without asthmatic granulomatosis showed more striking small airway injury, subbasement membrane thickening, and neutrophilic infiltrates. Cases with concurrent AID had a tendency to more parenchymal eosinophilic inflammation, more bronchiolocentric granulomas, and a suggestion of increased responsivity to nonsteroidal immunosuppressive therapy. Histologic examination of video-assisted thoracoscopic surgery lung biopsies in SA demonstrates diverse pathologies including cases associated with granulomatous inflammation in addition to eosinophilic infiltrates. This spectrum of histologies may link to a high incidence of AID.
Assuntos
Asma/patologia , Doenças Autoimunes/complicações , Bronquíolos/patologia , Granuloma/patologia , Adulto , Asma/complicações , Doenças Autoimunes/epidemiologia , Biópsia , Resistência a Medicamentos , Feminino , Granuloma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Cirurgia Torácica VídeoassistidaRESUMO
Merkel cell polyomavirus (MCPyV) is an oncogenic DNA virus that causes Merkel cell carcinoma. Recently, MCPyV has been identified in other noncutaneous tumors including lung non-small cell carcinoma. However, the true role of this virus in lung carcinogenesis is unclear. We aimed to determine the efficacy of immunohistochemistry for detecting MCPyV in a series of lung adenocarcinomas. Nuclear expression of the MCPyV large T antigen was evaluated by immunohistochemistry (CM2B4 antibody) in formalin-fixed paraffin-embedded lung adenocarcinomas of different histologic subtypes. Of a total of 90 lung adenocarcinomas that were examined, none of the tumors (0%) were positive for MCPyV T antigen expression by immunohistochemistry. These data suggest that MCPyV immunohistochemistry alone might not be a sensitive method for detection of MCPyV in lung adenocarcinomas or that these tumors do not harbor MCPyV. Further studies are needed to correlate these data with molecular studies for MCPyV DNA integration and to similarly evaluate other types of lung carcinomas.