Article
Virology
Julia M. DeRogatis, Emily N. Neubert, Karla M. Viramontes, Monique L. Henriquez, Dequina A. Nicholas, Roberto Tinoco
Summary: CD38 expression regulates the survival and metabolism of CD8(+) T cells during acute and chronic viral infections. Higher CD38 levels are observed during chronic infection, leading to T cell exhaustion. CD38 has a dual cell-intrinsic function in limiting proliferation and function while promoting the survival of CD8(+) T cells.
JOURNAL OF VIROLOGY
(2023)
Article
Biology
Risa Ebina-Shibuya, Erin E. West, Rosanne Spolski, Peng Li, Jangsuk Oh, Majid Kazemian, Daniel Gromer, Phillip Swanson, Ning Du, Dorian B. McGavern, Warren J. Leonard
Summary: TSLP plays a crucial role in the development of diseases such as asthma, atopic dermatitis, and allergic inflammation, but its role in CD8(+) T-cell primary responses and memory CD8(+) T cell responses to secondary viral infection is still controversial. Research has shown that TSLP limits the primary CD8(+) T-cell response to influenza, but has little effect on T cell function and the number of memory CD8(+) T cells generated after influenza infection, while inhibiting memory CD8(+) T-cell responses to secondary viral infections.
Article
Immunology
Avishai Shemesh, Yapeng Su, Daniel R. Calabrese, Daniel Chen, Janice Arakawa-Hoyt, Kole T. Roybal, James R. Heath, John R. Greenland, Lewis L. Lanier
Summary: This study reveals that diminished human NK cell proliferation contributes to the development of an adaptive-like NK cell phenotype in COVID-19 infection. The reduced expression of Fc epsilon RI gamma in NK cells is associated with increased inflammation and higher TGF beta and IFN alpha levels. The findings suggest that the adaptive-like NK cell phenotype and the levels of TGF beta and IFN alpha may serve as early prognostic markers for disease severity in COVID-19.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Rui Dai, Xiaopei Huang, Yiping Yang
Summary: This study demonstrates the critical role of gamma delta T cells in promoting the CD8(+) T cell response to VV infection. Gamma delta T cells are able to present viral antigens and activate CD8(+) T cells, with MyD88 signaling playing a key role in this process. Understanding the regulation of adaptive T cell response by gamma delta T cells may provide insight for the development of more effective vaccine strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jennifer Currenti, Becker M. P. Law, Kai Qin, Mina John, Mark A. Pilkinton, Anju Bansal, Shay Leary, Ramesh Ram, Abha Chopra, Rama Gangula, Ling Yue, Christian Warren, Louise Barnett, Eric Alves, Wyatt J. McDonnell, Anuradha Sooda, Sonya L. Heath, Simon Mallal, Paul Goepfert, Spyros A. Kalams, Silvana Gaudieri
Summary: Loss of T cell immunogenicity due to mutations in virally encoded epitopes is a well-described adaptation strategy to limit host anti-viral immunity. Another adaptation strategy, involving the selection of mutations within epitopes that retain immune recognition despite immune pressure, is less understood. This strategy may modulate the transcriptome of CD8(+) T cells and potentially select for less effective T cell clones over time.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jessica M. Sierra, Florencia Secchiari, Sol Y. Nunez, Ximena L. Raffo Iraolagoitia, Andrea Ziblat, Adrian D. Friedrich, Maria V. Regge, M. Cecilia Santilli, Nicolas I. Torres, Mariana Gantov, Aldana Trotta, Carlos Ameri, Gonzalo Vitagliano, Hernando Rios Pita, Luis Rico, Agustin Rovegno, Nicolas Richards, Carolina I. Domaica, Norberto W. Zwirner, Mercedes B. Fuertes
Summary: NK cells in clear cell renal cell carcinoma patients display altered phenotype and impaired effector functions, with a high frequency of tumor-infiltrating PD-L1(+) NK cells suggesting immunoregulatory functions. In vitro studies show that PD-L1(hi) NK cells exhibit an activated phenotype and enhanced effector functions, while also inhibiting CD8(+) T cell proliferation in a PD-L1-dependent manner.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Siyu Liu, Chang Xu, Fan Yang, Lu Zong, Yizu Qin, Yufeng Gao, Qian Su, Tuantuan Li, Ye Li, Yuanhong Xu, Meijuan Zheng
Summary: The antiviral response of NK cells and CD8(+) T cells is weak in patients with CHB, and the overexpression of Gal-9 contributes to NK cell dysfunction and CD8(+) T cell exhaustion. Blocking Gal-9 or TIM-3 can restore the function of CD8(+) T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Parva R. Thakker, Ardeshir J. Ariana, Stephanie R. Hajjar, David J. Cai, Dikchha R. Rijal, Subash J. Sad
Summary: XIAP is an endogenous inhibitor of cell death and inactivating mutations of XIAP are responsible for X-linked lymphoproliferative disease (XLP-2) and primary immunodeficiency. This study demonstrates that XIAP plays a crucial role in controlling cell death and regulating cytokine secretion during infection with intracellular bacteria. XIAP promotes the fitness and survival of activated CD8 T cells, but its deficiency leads to poor expansion, skewed differentiation, and a failure to control bacterial infection.
Article
Immunology
Shohei Harabuchi, Omar Khan, Hamid Bassiri, Taku Yoshida, Yohei Okada, Masaomi Takizawa, Osamu Ikeda, Akihiro Katada, Taku Kambayashi
Summary: This study investigates the role of TCR signaling pathways in chronic viral infection, revealing the distinct effects of DAG and ERK on CD8+ T cell activation and survival.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Valentina Tedeschi, Giorgia Paldino, Martina Kunkl, Marino Paroli, Rosa Sorrentino, Loretta Tuosto, Maria Teresa Fiorillo
Summary: CD8(+) T lymphocytes play a crucial role in immune response, but aging and disease can alter their function and phenotype, impacting vaccine and treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Amelie Rousseliere, Laurence Delbos, Celine Bressollette, Mailys Berthaume, Beatrice Charreau
Summary: This study quantitatively determined the frequency of various anti-HCMV immune cell subsets and qualitatively analyzed their phenotypes using spectral flow cytometry analysis. The results provide insights into the cellular immune responses to HCMV infection or vaccines, and can be used for monitoring and analysis of T-cell and NK cell responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Maria B. Bordignon, Ayelen I. Pesce Viglietti, Estefania P. Julia, Maria B. Sanchez, Alexander Roelle, Pablo Mando, Luciana Sabatini, Alexis Ostinelli, Manglio M. Rizzo, Maria M. Barrio, Jose Mordoh, Leonardo Fainboim, Estrella M. Levy
Summary: Adaptive NK cells, which expand after HCMV infection, have stronger cytokine production, longer life and persistence compared to conventional NK cells, making them valuable for cancer immunotherapy. In this study, adaptive NK cell subpopulations were characterized in HER2+ breast cancer patients and found to overlap to a lesser extent than in healthy donors. However, no significant phenotypic differences were observed between patients and donors. Additionally, the presence of both Fc epsilon RI gamma- and NKG2C+ was necessary for increased IFN-gamma production in patients, while the presence of NKG2C alone was sufficient in donors. These findings suggest that adaptive NK cell subsets may play a role in therapeutic approaches targeting tumor antigens.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Microbiology
Sebastian Klein, Jasmin Mischke, Finn Beruldsen, Immo Prinz, Dinler A. Antunes, Markus Cornberg, Anke R. M. Kraft
Summary: A hallmark of chronic viral infections is exhausted antigen-specific CD8(+) T cell responses and the persistence of the virus in the immune system. This study aimed to examine the variability of epitope-specific T cell exhaustion and its relationship to T cell receptor (TCR) repertoire in a chronic setting with immune checkpoint inhibitor therapy. The results showed that there were individual and independent responses within one immune response, with different levels of exhaustion and TCR repertoire diversity. Additionally, the study revealed that immune checkpoint inhibitor therapy had heterogeneous effects on the TCR repertoire of different epitope-specific T cell responses. These findings have important implications for therapeutic approaches targeting chronic viral infections.
Article
Microbiology
Maura Statzu, Guido Silvestrl
Summary: Cytotoxic CD8(+) T cells can decrease the lifespan of infected cells during acute simian immunodeficiency virus infection, but they are unable to prevent the establishment of a persistent reservoir of latently infected cells under long-term antiretroviral therapy.
NATURE MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nana Afia Asante Ntim, Hiroshi Ishii, Moe Jomori, Hiroyuki Yamamoto, Tetsuro Matano, Takushi Nomura
Summary: CD8(+) T-cell responses play an important role in suppressing viral replication and selecting for viral escape mutations in HIV infection. This study investigated the sequential selection of viral mutations in CD8(+) T-cell epitope-coding regions in a simian AIDS model. The results showed that viral mutations were selected in multiple epitope-coding regions, and the number of mutated regions was associated with viral loads.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Yuan Zhuang, Haifeng C. Xu, Prashant V. Shinde, Jens Warfsmann, Jelena Vasilevska, Balamurugan Sundaram, Kristina Behnke, Jun Huang, Jessica I. Hoell, Arndt Borkhardt, Klaus Pfeffer, Mohamed S. Taha, Diran Herebian, Ertan Mayatepek, Dirk Brenner, Mohammad Reza Ahmadian, Verena Keitel, Dagmar Wieczorek, Dieter Haeussinger, Aleksandra A. Pandyra, Karl S. Lang, Philipp A. Lang
Article
Oncology
Wei Liu, Pawel Stachura, Haifeng C. Xu, Nikkitha Umesh Ganesh, Fiona Cox, Ruifeng Wang, Karl S. Lang, Jay Gopalakrishnan, Dieter Haeussinger, Bernhard Homey, Philipp A. Lang, Aleksandra A. Pandyra
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2020)
Article
Immunology
Philipp A. Lang, Sarah Q. Crome, Haifeng C. Xu, Karl S. Lang, Laurence Chapatte, Elissa K. Deenick, Melanie Grusdat, Aleksandra A. Pandyra, Vitaly Pozdeev, Ruifeng Wang, Tobias A. W. Holderried, Harvey Cantor, Andreas Diefenbach, Alisha R. Elford, David R. McIlwain, Mike Recher, Dieter Haeussinger, Tak W. Mak, Pamela S. Ohashi
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2020)
Article
Microbiology
Thamer A. Hamdan, Hilal Bhat, Lamin B. Cham, Tom Adomati, Judith Lang, Fanghui Li, Ali Murtaza, Cornelia Hardt, Philipp A. Lang, Vikas Duhan, Karl S. Lang
Review
Microbiology
Thamer A. Hamdan, Philipp A. Lang, Karl S. Lang
Article
Multidisciplinary Sciences
Judith Lang, Patrick Bohn, Hilal Bhat, Holger Jastrow, Bernd Walkenfort, Feyza Cansiz, Julian Fink, Michael Bauer, Dominik Olszewski, Ana Ramos-Nascimento, Vikas Duhan, Sarah-Kim Friedrich, Katrin Anne Becker, Adalbert Krawczyk, Michael J. Edwards, Andreas Burchert, Magdalena Huber, Justa Friebus-Kardash, Joachim R. Goethert, Cornelia Hardt, Hans Christian Probst, Fabian Schumacher, Karl Koehrer, Burkhard Kleuser, Eduard B. Babiychuk, Beate Sodeik, Juergen Seibel, Urs F. Greber, Philipp A. Lang, Erich Gulbins, Karl S. Lang
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Tom Adomati, Lamin B. Cham, Thamer A. Hamdan, Hilal Bhat, Vikas Duhan, Fanghui Li, Murtaza Ali, Elisabeth Lang, Anfei Huang, Eyad Naser, Vishal Khairnar, Sarah-Kim Friedrich, Judith Lang, Justa Friebus-Kardash, Michael Bergerhausen, Maximilian Schiller, Yara Maria Machlah, Florian Lang, Dieter Haeussinger, Stanislav Ferencik, Cornelia Hardt, Philipp A. Lang, Karl S. Lang
Article
Immunology
Sarah-Kim Friedrich, Rosa Schmitz, Michael Bergerhausen, Judith Lang, Lamin B. Cham, Vikas Duhan, Dieter Haeussinger, Cornelia Hardt, Marylyn Addo, Marco Prinz, Kenichi Asano, Philipp Alexander Lang, Karl Sebastian Lang
Article
Immunology
Vikas Duhan, Vishal Khairnar, Simo Kitanovski, Thamer A. Hamdan, Andres D. Klein, Judith Lang, Murtaza Ali, Tom Adomati, Hilal Bhat, Sarah-Kim Friedrich, Fanghui Li, Philippe Krebs, Anthony H. Futerman, Marylyn M. Addo, Cornelia Hardt, Daniel Hoffmann, Philipp A. Lang, Karl S. Lang
Summary: In this study, CD103 was identified as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 specifically expressed by splenic conventional dendritic cells (cDCs) limited IFN-I production through suppressing AKT phosphorylation and mTOR activation in DCs during VSV infection, which accelerated early IFN-I in cDCs and prevented death in VSV infected animals.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Vikas Duhan, Mark J. Smyth
Summary: Cancer immunotherapies are increasingly approved in the clinic, but only a fraction of patients benefit long-term. Understanding the mechanisms of immunotherapeutic resistance is critical for broader utility and benefit of cancer immunotherapy. Tumor infiltrating myeloid cells play a critical role in regulating anti-tumor lymphocyte effector cells in the tumor microenvironment.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Microbiology
Sarah-Kim Friedrich, Rosa Schmitz, Michael Bergerhausen, Judith Lang, Vikas Duhan, Cornelia Hardt, Matthias Tenbusch, Marco Prinz, Kenichi Asano, Hilal Bhat, Thamer A. Hamdan, Philipp Alexander Lang, Karl Sebastian Lang
Summary: The replication of Influenza A virus in secondary lymphatic organs leads to innate immune activation, which is dependent on the expression of Sialic acid residues in antigen-presenting cells and the interferon-inhibitor UBP43 (Usp18).