Review
Immunology
Rami Bechara, Alexia Feray, Marc Pallardy
Summary: Allergic reactions to drugs and chemicals are mediated by specific T cells and it is unclear whether there is a common occurrence of thymic selection of drug/chemical-specific T cells. Recent observations suggest that T-cell receptor recognition of hapten-modified peptides may play a crucial role in drug/chemical allergy. This understanding could lead to efficient strategies for allergy diagnosis and predicting the immunogenic potential of new chemicals.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ainsley Lockhart, Aubrey Reed, Tiago Rezende de Castro, Calvin Herman, Maria Cecilia Campos Canesso, Daniel Mucida
Summary: The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4(+) T cells. Combining antigenically defined diets with gnotobiotic models, the study shows that both food and microbiota have distinct effects on the profile and T cell receptor repertoire of intestinal CD4(+) T cells. The response of CD4(+) T cells to food is disrupted by inflammatory challenge, but protection against food allergy is associated with Treg clonal expansion and decreased proinflammatory gene expression.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Oncology
Asaf Maoz, Carter Merenstein, Yusuke Koga, Austin Potter, Adam C. Gower, Gang Liu, Sherry Zhang, Hanqiao Liu, Christopher Stevenson, Avrum Spira, Mary E. Reid, Joshua D. Campbell, Sarah A. Mazzilli, Marc E. Lenburg, Jennifer Beane
Summary: This study characterized the T cell receptor repertoire in bronchial premalignant lesions (PMLs) using RNA-seq data, revealing an association between TCR diversity and immune activation signatures in PMLs. The study also found differences in TCR diversity between regressive and progressive/persistent PMLs and identified shared TCR sequences with potential antigen specificities in PML samples.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Svitlana Skoroplyas, Ondrej Vasicek, Michaela Chorvatova, Petra Dad'ova, Katerina Lehka, Lukas Kubala
Summary: Pseurotin D has the potential to inhibit DTH reaction through inhibiting the activation and differentiation of both T cells and B cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Biochemistry & Molecular Biology
Mu-Tzu Chu, Wan-Chun Chang, Shih-Cheng Pao, Shuen-Iu Hung
Summary: Drug hypersensitivity reactions can be immediate or delayed. Delayed drug hypersensitivity is mainly caused by T lymphocyte recognition of drug antigens and cell activation. This type of hypersensitivity can have various clinical presentations ranging from mild reactions to severe cutaneous adverse reactions. Common culprits of delayed drug hypersensitivity include anti-epileptics, antibiotics, anti-gout agents, and anti-viral drugs. The pathogenesis involves molecular recognition, genetic susceptibility, and immune mediators.
Article
Oncology
Brie Chun, Joanna Pucilowska, ShuChing Chang, Isaac Kim, Benjamin Nikitin, Yoshinobu Koguchi, William L. Redmond, Brady Bernard, Venkatesh Rajamanickam, Nathan Polaske, Paul A. Fields, Valerie Conrad, Mark Schmidt, Walter J. Urba, Alison K. Conlin, Heather L. McArthur, David B. Page
Summary: This study investigates the effects of pembrolizumab combined with paclitaxel or capecitabine on T-cell subsets in triple-negative breast cancer patients. The results show that these treatments result in similar lymphodepletions across peripheral T-cell subsets and do not alter T-cell clonal diversity. The findings contribute to our understanding of the impact of chemoimmunotherapy on the immune system.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Pavel Shelyakin, Ksenia R. Lupyr, Evgeny S. Egorov, Ilya A. Kofiadi, Dmitriy B. Staroverov, Sofya A. Kasatskaya, Valeriia V. Kriukova, Irina A. Shagina, Ekaterina M. Merzlyak, Tatiana O. Nakonechnaya, Elena A. Latysheva, Irina A. Manto, Musa R. Khaitov, Sergey A. Lukyanov, Dmitriy M. Chudakov, Olga Britanova
Summary: The interplay between T- and B-cell compartments during naive, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. The findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naive Treg TCR repertoire that enables better control of self-reactive T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Xuan Zhao, Zhen Zhang, Chunli Wen, Jianmin Huang, Shuangning Yang, Jinyan Liu, Huizhen Geng, Bing Peng, Zibo Li, Yi Zhang
Summary: This study demonstrates that multiple peptide-pulsed DCs combined with CTLs therapy has manageable safety and promising efficacy for cancer patients, which might provide a precise immunotherapeutic strategy for cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Shawn H. R. Lee, Zhenhua Li, Evelyn H. Z. Lim, Winnie H. N. Chin, Nan Jiang, Kean Hui Chiew, Zhiwei Chen, Bernice L. Z. Oh, Ah Moy Tan, Hany Ariffin, Jun J. Yang, Allen E. J. Yeoh
Summary: The aim of this study was to investigate the association between T-cell receptor (TCR) repertoire diversity and the risk of allergy. The study found that patients with a more diverse and dynamically changing TCR repertoire had an increased risk of allergy and decreased asparaginase activity. A higher variability of the repertoire between timepoints predicted the occurrence of allergy. After allergy occurred, the TCR repertoire became more similar. Understanding the immunological basis of this common toxicity in childhood acute lymphoblastic leukemia (ALL) can help in developing better methods to predict or manage this event.
Article
Immunology
Luis Weitbrecht, Daniel Berchtold, Tian Zhang, Sandra Jagdmann, Claudia Dames, Katarzyna Winek, Christian Meisel, Andreas Meisel
Summary: The study revealed that CD4(+) T cells play a crucial role in facilitating delayed B cell infiltration into the ischemic brain post-stroke, highlighting the long-lasting impact of lymphocyte infiltration on immune response. Depletion of CD4 T cells improved cognitive functions, suggesting the potential of specific immune modulating therapies for treating post-stroke cognitive impairment.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Oncology
Mizuki Haraguchi, Kazuma Kiyotani, Tomohiro Tate, Seiji Sakata, Ray Sagawa, Satoshi Takagi, Satoshi Nagayama, Kengo Takeuchi, Kazuhisa Takahashi, Ryohei Katayama
Summary: Immune checkpoint inhibitors (ICIs) have shown significant clinical responses and improved overall survival for various cancers. However, response to ICI therapy varies among patients. This study established a mouse model to better understand the host immune response to tumors and the role of T cells in ICI therapy. The study also identified shared T cell receptors (TCR) in colorectal cancer (CRC) patients. The results suggest that memory T cells play a crucial role in the immune response to tumors and the established model has potential for studying systemic memory T cell behavior.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Hiroyasu Aoki, Satoshi Ueha, Shigeyuki Shichino, Haru Ogiwara, Kohei Shitara, Manami Shimomura, Toshihiro Suzuki, Tetsuya Nakatsura, Makiko Yamashita, Shigehisa Kitano, Sakiko Kuroda, Masashi Wakabayashi, Makoto Kurachi, Satoru Ito, Toshihiko Doi, Kouji Matsushima
Summary: Transient depletion of CD4(+) cells leads to replacement of T-cell clones in the blood, which is associated with the extent of CD4(+) T-cell depletion and an increase in CD8(+) T-cell count. This clonal replacement of the TCR repertoire is linked to the expansion of tumor-reactive T-cell clones and antitumor responses.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Medicine, Research & Experimental
Jeff W. Chen, Jean-Nicolas Schickel, Nikolaos Tsakiris, Joel Sng, Florent Arbogast, Delphine Bouis, Daniele Parisi, Ruchi Gera, Joshua M. Boeckers, Fabien R. Delmotte, Margaret Veselits, Catharina Schuetz, Eva-Maria Jacobsen, Carsten Posovszky, Ansgar S. Schulz, Klaus Schwarz, Marcus R. Clark, Laurence Menard, Eric Meffre
Summary: Using humanized mouse models, it was observed that there is a strong skewing of the expressed immunoglobulin repertoire upon transit into the peripheral naive B cell pool. Positive selection of expanded naive B cells is beneficial, while negative selection of autoreactive B cells requires the involvement of regulatory T cells.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Adam M. Swartz, Kendra L. Congdon, Smita K. Nair, Qi-Jing Li, James E. Herndon, Carter M. Suryadevara, Katherine A. Riccione, Gary E. Archer, Pamela K. Norberg, Luis A. Sanchez-Perez, John H. Sampson
Summary: This study shows that therapeutic vaccines targeting immunodominant MHC I-restricted neoepitopes require a conjoined helper epitope to induce a cytotoxic CD8+ T-cell response, and the universally immunogenic helper epitope P30 can fulfill this function. Moreover, the conjoined P30 can improve immune and antitumor responses to subdominant MHC I-restricted neoepitopes that are poorly immunogenic. These findings provide insights into effective neoantigen vaccine design and suggest a translational strategy to enhance therapeutic responses to MHC I-restricted neoepitopes.
Review
Chemistry, Medicinal
Paul Thomson, Sean Hammond, Xiaoli Meng, Dean J. Naisbitt
Summary: The relationship between drug protein adduct formation and development of immunological adverse drug reactions has been a topic of active research for over 80 years. The hapten hypothesis proposes that the immunogenicity of small organic chemicals depends on modification of self-proteins, and this hypothesis has expanded to include drugs that generate reactive intermediates. Although the pathway of hapten-specific T-cell activation is well established, there are still unanswered questions regarding the nature of hapten-modified peptides, the number of peptides that stimulate T-cells, the critical protein modifications involved in T-cell activation, and the role of hapten-specific T-cells in iatrogenic disease.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Review
Allergy
Dean J. Naisbitt, Anna Olsson-Brown, Andrew Gibson, Xiaoli Meng, Monday O. Ogese, Arun Tailor, Paul Thomson
Article
Allergy
Paul J. Thomson, Patricia T. Illing, John Farrell, Mohammad Alhaidari, Catherine C. Bell, Neil Berry, Paul M. O'Neill, Anthony W. Purcell, Kevin B. Park, Dean J. Naisbitt
Review
Chemistry, Medicinal
Sean Hammond, Paul J. Thomson, Monday O. Ogese, Dean J. Naisbitt
CHEMICAL RESEARCH IN TOXICOLOGY
(2020)
Article
Allergy
Adriana Ariza, Ruben Fernandez-Santamaria, Xiaoli Meng, Maria Salas, Monday O. Ogese, Arun Tailor, Gador Bogas, Maria Jose Torres, Dean J. Naisbitt
Article
Toxicology
Monday O. Ogese, Joel Watkinson, Adam Lister, Lee Faulkner, Andrew Gibson, Aimee Hillegas, Melanie Z. Sakatis, Brian Kevin Park, Dean J. Naisbitt
TOXICOLOGICAL SCIENCES
(2020)
Editorial Material
Gastroenterology & Hepatology
Sandra De Jonghe, Daniel Weinstock, Jason Aligo, Kay Washington, Dean Naisbitt
Article
Allergy
Jobst F. Roehmel, Monday O. Ogese, Alexander Rohrbach, Marcus A. Mall, Dean J. Naisbitt
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Toxicology
James C. Waddington, Xiaoli Meng, Patricia T. Illing, Arun Tailor, Kareena Adair, Paul Whitaker, Jane Hamlett, Rosalind E. Jenkins, John Farrell, Neil Berry, Anthony W. Purcell, Dean J. Naisbitt, Brian Kevin Park
TOXICOLOGICAL SCIENCES
(2020)
Article
Toxicology
Arun Tailor, Xiaoli Meng, Kareena Adair, John Farrell, James C. Waddington, Ann Daly, Munir Pirmohamed, Gordon Dear, B. Kevin Park, Dean J. Naisbitt
TOXICOLOGICAL SCIENCES
(2020)
Article
Chemistry, Medicinal
Andrew Gibson, Sean Hammond, Kanoot Jaruthamsophon, Sharin Roth, Merrie Mosedale, Dean J. Naisbitt
CHEMICAL RESEARCH IN TOXICOLOGY
(2020)
Article
Immunology
Monday O. Ogese, Adam Lister, Rosalind E. Jenkins, Xiaoli Meng, Ana Alfirevic, Lisa Douglas, Rachel Mcloughlin, Edward Silva, B. Kevin Park, Munir Pirmohamed, Dean J. Naisbitt
JOURNAL OF IMMUNOLOGY
(2020)
Article
Toxicology
Sean Hammond, Andrew Gibson, Kanoot Jaruthamsophon, Sharin Roth, Merrie Mosedale, Dean J. Naisbitt
Summary: Exposure to tolvaptan is associated with a significant risk of liver injury, potentially due to an adaptive immune attack. The study suggests that tolvaptan and metabolite-specific T cells may be candidate effector cells in such injury.
TOXICOLOGICAL SCIENCES
(2021)
Article
Allergy
Paul J. Thomson, Laila Kafu, Xiaoli Meng, Jan Snoeys, An De Bondt, Dries De Maeyer, Hans Wils, Laurent Leclercq, Petra Vinken, Dean J. Naisbitt
Summary: The study aimed to generate and characterize atabecestat(metabolite)-responsive T-cell clones from patients with liver injury. CD4(+) T-cell clones activated via a pharmacological interactions pathway in patients with liver injury suggest an immune-based mechanism for the observed hepatic enzyme elevations.
Article
Immunology
Ryan G. Nattrass, Lisa Krafft, Polina Zjablovskaja, Marc Schuster, Bahram Kasmapour, Cem Sarisoy, Jessica Minich, Elena Bach, Hendrik Streeck
Summary: Age is associated with increased risk of severe COVID-19 and changes in SARS-CoV-2-reactive CD4 T cells in individuals recovered from COVID-19. Older individuals have higher numbers of SARS-CoV-2-reactive T cells and highly polyfunctional T cells after recovery, compared to younger individuals. These responses persist over time, suggesting a potential role of age in immune response to SARS-CoV-2.
Article
Chemistry, Medicinal
James C. Waddington, Serat-E Ali, Sophie L. Penman, Paul Whitaker, Jane Hamlett, Amy Chadwick, Dean J. Naisbitt, B. Kevin Park, Xiaoli Meng
CHEMICAL RESEARCH IN TOXICOLOGY
(2020)
