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1.
J Immunol ; 213(5): 588-599, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38975728

RESUMO

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on Ag-specific CD8+ short-lived effector cells, while it's co-ectoenzyme, CD73, is found on memory precursor effector cells (MPECs) in vivo. Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory T cell (TRM cell) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine TRM cells across several nonlymphoid tissues and melanoma, whereas CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ TRM cells are fully functional when stimulated ex vivo with cognate Ag, further expanding the identity of CD39 beyond a T cell exhaustion marker.


Assuntos
Antígenos CD , Apirase , Linfócitos T CD8-Positivos , Diferenciação Celular , Células T de Memória , Animais , Apirase/imunologia , Apirase/metabolismo , Camundongos , Linfócitos T CD8-Positivos/imunologia , Antígenos CD/metabolismo , Antígenos CD/imunologia , Humanos , Células T de Memória/imunologia , Diferenciação Celular/imunologia , Memória Imunológica/imunologia , Camundongos Endogâmicos C57BL , 5'-Nucleotidase/metabolismo , 5'-Nucleotidase/imunologia
2.
Surg Neurol Int ; 15: 55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468685

RESUMO

Background: Composite hemangioendothelioma (CHE) is a rare, locally aggressive neoplasm of intermediate malignant potential. It is composed of a mixture of vascular tumors with a predilection for the dermis and subcutis of the extremities. Case Description: In this report, we describe a 41-year-old man who presented with a 2-month history of headache, dizziness, and intermittent seizures. Magnetic resonance imaging showed a hemorrhagic, multilobulated, and dural-based mass with extension into the calvarium. The mass measured 10.3 × 4.8 × 4 cm along the interhemispheric fissure and encased the superior sagittal sinus. Excision was performed, and histopathologic examination revealed a heterogeneous mixture of vascular components consisting of epithelioid hemangioendothelioma, retiform hemangioendothelioma, and hemangioma. This is the first report of a primary intracranial CHE. Conclusion: The spectrum of mesenchymal neoplasms within the cranium expands to encompass CHE.

3.
bioRxiv ; 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38559200

RESUMO

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on antigen-specific CD8+ short-lived effector cells (SLECs), while it's co-ecto-enzyme, CD73, is found on memory precursor effector cells (MPEC) in vivo . Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory (T RM ) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine T RM across several non-lymphoid tissues and melanoma, while CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ T RM are fully functional when stimulated ex vivo with cognate antigen. This work further expands the identity of CD39 beyond a T cell exhaustion marker.

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