Brain-resident memory CD8+ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation.
Ilija Brizić,Božo Šušak,Božo Šušak,Maja Arapović,Maja Arapović,Peter C. Huszthy,Peter C. Huszthy,Lea Hiršl,Daria Kveštak,Vanda Juranić Lisnić,Mijo Golemac,Ester Pernjak Pugel,Jelena Tomac,Annetrte Oxenius,William J. Britt,Jurica Arapović,Jurica Arapović,Astrid Krmpotić,Stipan Jonjić +18 more
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TLDR
It is shown that CD8+ T cells infiltrate the brain and form a pool of tissue‐resident memory T cells (TRM cells) that persist for lifetime, which provide protection against primary MCMV infection in newborn mice, reduce brain pathology, and remain in the brain as TRM cells.Abstract:
Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with mouse cytomegalovirus (MCMV) intraperitoneally is a well-established model of congenital human cytomegalovirus infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here, we used this model to investigate the role, dynamics, and phenotype of CD8+ T cells in the brain following infection of newborn mice. We show that CD8+ T cells infiltrate the brain and form a pool of tissue-resident memory T cells (TRM cells) that persist for lifetime. Adoptively transferred virus-specific CD8+ T cells provide protection against primary MCMV infection in newborn mice, reduce brain pathology, and remain in the brain as TRM cells. Brain CD8+ TRM cells were long-lived, slowly proliferating cells able to respond to local challenge infection. Importantly, brain CD8+ TRM cells controlled latent MCMV and their depletion resulted in virus reactivation and enhanced inflammation in brain.read more
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Tissue-resident memory T cells populate the human brain
Joost Smolders,Kirstin M. Heutinck,Nina L. Fransen,Ester B. M. Remmerswaal,Pleun Hombrink,Ineke J. M. ten Berge,René A. W. van Lier,Inge Huitinga,Jörg Hamann,Jörg Hamann +9 more
TL;DR: It is concluded that the human brain is surveilled by TRM cells, providing protection against neurotropic virus reactivation, whilst being under tight control of key immune checkpoint molecules.
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Tissue-resident lymphocytes: from adaptive to innate immunity
TL;DR: The recent findings on the tissue residency of both innate and adaptive lymphocytes are discussed, with a particular focus on CD8+ memory T cells, and some advances regarding unconventional T cells (invariant NKT cells, mucosal-associated invariant T Cells (MAIT), and γδ T cells) and the emerging family of trNK cells are described.
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The role of T cells in the pathogenesis of Parkinson's disease.
TL;DR: It is concluded that abnormal T cell‐mediated immunity is a fundamental pathological process that may be a promising translational therapeutic target for Parkinson’s disease.
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Long-term persistence of infectious Zika virus: Inflammation and behavioral sequela in mice.
Derek D. C. Ireland,Mohanraj Manangeeswaran,Aaron P. Lewkowicz,Kaliroi Engel,Sarah M. Clark,Adelle Laniyan,Jacob Sykes,Ha-Na Lee,Ian L. McWilliams,Logan Kelley-Baker,Leonardo H. Tonelli,Daniela Verthelyi +11 more
TL;DR: Although the infection appears to persist in defined reservoirs within CNS, the resulting inflammation could increase the risk of neurodegenerative disorders and raises concern regarding possible long-term effects in asymptomatic children exposed to the virus.
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Brain-Resident T Cells Following Viral Infection.
TL;DR: It is demonstrated that the brain microenvironment, both during and following inflammation, prominently contributes to the role of CD103 in T cell persistence, and shows that microglia, and astrocytes, upregulate programmed death ligand 1 during neuroinflammation, and the PD-1: PD-L1 pathway also aids in bTRM generation and retention.
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Journal ArticleDOI
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
TL;DR: It is shown that expression of CCR7, a chemokine receptor that controls homing to secondary lymphoid organs, divides human memory T cells into two functionally distinct subsets, which are named central memory (TCM) and effector memory (TEM).
Journal ArticleDOI
T cell receptor antagonist peptides induce positive selection
Kristin A. Hogquist,Stephen C. Jameson,William R. Heath,Jane L Howard,Michael J. Bevan,Francis R. Carbone +5 more
TL;DR: Results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.
Journal ArticleDOI
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Mehrdad Matloubian,Charles G. Lo,Guy Cinamon,Matthew J. Lesneski,Ying Xu,Volker Brinkmann,Maria L. Allende,Richard L. Proia,Jason G. Cyster +8 more
TL;DR: It is established that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.
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Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes.
TL;DR: The CD8+ effector cells raised in the CD4 subset- deficient host were able of clear vital tissues from productive infection and to restrict asymptomatic, persistent infection to acinar glandular epithelial cells in salivary gland tissue.
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Preferential Localization of Effector Memory Cells in Nonlymphoid Tissue
TL;DR: In response to viral or bacterial infection, antigen-specific CD8 T cells migrated to nonlymphoid tissues and were present as long-lived memory cells, pointing to the existence of a population of extralymphoid effector memory T cells poised for immediate response to infection.