scholarly journals Formation and Maintenance of Tissue Resident Memory CD8+ T Cells after Viral Infection

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 196 ◽  
Author(s):  
David J. Topham ◽  
Emma C. Reilly ◽  
Kris Lambert Emo ◽  
Mike Sportiello
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Vaccine Development ◽  
Protective Role ◽  
Lymphoid Tissues ◽  
Extrinsic Factors ◽  
Memory Cd8 T Cells ◽  
Peptide Epitopes ◽  
Different Strains ◽  
Immune Subset

Tissue resident memory (TRM) CD8 T cells comprise a memory population that forms in peripheral, non-lymphoid tissues after an infection that does not recirculate into the bloodstream or other tissues. TRM cells often recognize conserved peptide epitopes shared among different strains of a pathogen and so offer a protective role upon secondary encounter with the same or related pathogens. Several recent studies have begun to shed light on the intrinsic and extrinsic factors regulating TRM. In addition, work is being done to understand how canonical “markers” of TRM actually affect the function of these cells. Many of these markers regulate the generation or persistence of these TRM cells, an important point of study due to the differences in persistence of TRM between tissues, which may impact future vaccine development to cater towards these important differences. In this review, we will discuss recent advances in TRM biology that may lead to strategies designed to promote this important protective immune subset.

scholarly journals Resident memory CD8 T cells persist for years in human small intestine

2019 ◽  
Vol 216 (10) ◽  
pp. 2412-2426 ◽  
Author(s):  
Raquel Bartolomé-Casado ◽  
Ole J.B. Landsverk ◽  
Sudhir Kumar Chauhan ◽  
Lisa Richter ◽  
Danh Phung ◽  
...  
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
Lamina Propria ◽  
Cd8 T Cells ◽  
Vaccine Development ◽  
Oral Vaccines ◽  
Memory Cd8 T Cells ◽  
Immune Mediated ◽  
Tnf Α ◽  
Bona Fide

Resident memory CD8 T (Trm) cells have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI, we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for >1 yr in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine producers, exhibiting a polyfunctional (IFN-γ+ IL-2+ TNF-α+) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.

scholarly journals Route of Immunization with Peptide-pulsed Dendritic Cells Controls the Distribution of Memory and Effector T Cells in Lymphoid Tissues and Determines the Pattern of Regional Tumor Control

2003 ◽  
Vol 198 (7) ◽  
pp. 1023-1034 ◽  
Author(s):  
David W. Mullins ◽  
Stacey L. Sheasley ◽  
Rebecca M. Ream ◽  
Timothy N.J. Bullock ◽  
Yang-Xin Fu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Lung Metastases ◽  
Memory Cell ◽  
Lung Tumors ◽  
Tumor Control ◽  
Lymphoid Tissues ◽  
Memory Cd8 T Cells ◽  
And Control

We have established that the route of immunization with peptide-pulsed, activated DC leads to memory CD8+ T cells with distinct distributions in lymphoid tissues, which determines the ability to control tumors growing in different body sites. Both intravenous (i.v.) and subcutaneous (s.c.) immunization induced memory T cells in spleen and control of metastatic-like lung tumors. s.c. immunization also induced memory T cells in lymph nodes (LNs), imparting protection against subcutaneously growing tumors. In contrast, i.v. immunization-induced memory was restricted to spleen and failed to impart protective immunity against subcutaneously growing tumors. Memory cell distribution and tumor control were both linked to injection route–dependent localization of DCs in lymphoid compartments. Using peripheral LN–ablated mice, these LNs were shown to be essential for control of subcutaneously growing tumors but not lung metastases; in contrast, using immunized asplenic mice, we found that the spleen is necessary and sufficient for control of lung tumors, but unnecessary for control of subcutaneously growing tumors. These data demonstrate the existence of a previously undescribed population of splenic-resident memory CD8 T cells that are essential for the control of lung metastases. Thus, regional immunity based on memory T cell residence patterns is an important factor in DC-based tumor immunotherapy.

scholarly journals Memory CD8+ T Cells Are Required for Protection from Persistent Hepatitis C Virus Infection

2003 ◽  
Vol 197 (12) ◽  
pp. 1645-1655 ◽  
Author(s):  
Naglaa H. Shoukry ◽  
Arash Grakoui ◽  
Michael Houghton ◽  
David Y. Chien ◽  
John Ghrayeb ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Protective Role ◽  
Cytolytic Activity ◽  
Memory Cd8 T Cells ◽  
Rapid Acquisition ◽  
Virus Clearance

Few hepatitis C virus (HCV) infections resolve spontaneously but those that do appear to afford protective immunity. Second infections are usually shorter in duration and are less likely to persist but mechanisms of virus control in immune individuals have not been identified. In this study we investigated whether memory helper and/or cytotoxic T lymphocytes provide protection in chimpanzees serially reinfected with the virus. Clearance of the first infection took 3–4 mo and coincided with the delayed onset of CD4+ and CD8+ T cell responses. High frequencies of memory T cells targeting multiple HCV proteins were stable over 7 yr of follow-up. Animals were infected for a second time to assess the protective role of memory T cells. In contrast to the prolonged course of the first infection, viremia was terminated within 14 d. Control of this second infection was kinetically linked to rapid acquisition of virus-specific cytolytic activity by liver resident CD8+ T cells and expansion of memory CD4+ and CD8+ T cells in blood. The importance of memory CD8+ T cells in control of HCV infection was confirmed by antibody-mediated depletion of this lymphocyte subset before a third infection. Virus replication was prolonged despite the presence of memory CD4+ T helper cells primed by the two prior infections and was not terminated until HCV-specific CD8+ T cells recovered in the liver. These experiments demonstrate an essential role for memory CD8+ T cells in long-term protection from chronic hepatitis C.

scholarly journals SMAD4 and TGFβ are architects of inverse genetic programs during fate-determination of antiviral memory CD8 T cells

2021 ◽  
Author(s):  
Karthik Chandiran ◽  
Jenny Suarez-Ramirez ◽  
Yinghong Hu ◽  
Zeynep Ugur ◽  
Evan R Jellison ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Lymphoid Tissues ◽  
Peripheral Tissues ◽  
Memory Cd8 T Cells ◽  
Specific Memory ◽  
Smad Proteins

Transforming growth factor β (TGFβ) is a morphogenic protein that augments antiviral immunity by altering the functional properties of pathogen-specific memory CD8 T cells. During infection, TGFβ inhibits formation of effector (TEFF) and circulating memory CD8 T cells, while encouraging tissue resident memory CD8 T cells (TRM) to settle in peripheral tissues. SMAD proteins are signaling intermediates that are used by members of the TGF cytokine family to modify gene expression. Using RNA-sequencing we determined that SMAD4 altered the transcriptional profile of antiviral CTLs during respiratory infection. Our data show that SMAD4 and TGFβ use alternate signaling pathways to cooperatively regulate a collection of genes that determine whether pathogen-specific memory CD8 T cells localize in peripheral or lymphoid tissues. During infection, SMAD4 acts independently of TGFβ to inhibit TRM development, while inducing genes that support formation of circulating memory CD8 T cells. The genes that are modulated by SMAD4 include several homing receptors (CD103, KLRG1 and CD62L) and transcription factors (Hobit and EOMES) that support memory formation.

scholarly journals Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Brandon J. Burbach ◽  
Stephen D. O’Flanagan ◽  
Qi Shao ◽  
Katharine M. Young ◽  
Joseph R. Slaughter ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Irreversible Electroporation ◽  
Vaccination Strategy ◽  
Dual Therapy ◽  
Lymphoid Tissues ◽  
Tumor Challenge ◽  
Memory Cd8 T Cells ◽  
Tumor Destruction ◽  
Specific Tissue

AbstractMemory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory T cells (TRM) during cancer immunotherapy. Using a transplantable mouse model of prostate carcinoma, here we report that tumor challenge leads to expansion of naïve neoantigen-specific CD8+ T cells and formation of a small population of non-recirculating TRM in several NLTs. Primary tumor destruction by irreversible electroporation (IRE), followed by anti-CTLA-4 immune checkpoint inhibitor (ICI), promotes robust expansion of tumor-specific CD8+ T cells in blood, tumor, and NLTs. Parabiosis studies confirm that TRM establishment following dual therapy is associated with tumor remission in a subset of cases and protection from subsequent tumor challenge. Addition of anti-PD-1 following dual IRE + anti-CTLA-4 treatment blocks tumor growth in non-responsive cases. This work indicates that focal tumor destruction using IRE combined with ICI is a potent in situ tumor vaccination strategy that generates protective tumor-specific TRM.

Antigen cross-presentation in the liver generates protective memory CD8+ T cells in the absence of inflammation

2012 ◽  
Vol 50 (01) ◽  
Author(s):  
JP Böttcher ◽  
D Stabenow ◽  
S Debey-Pascher ◽  
A Staratschek-Jox ◽  
J Grell ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells ◽  
Cross Presentation
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