Article
Multidisciplinary Sciences
Amelie Cachot, Mariia Bilous, Yen-Cheng Liu, Xiaokang Li, Margaux Saillard, Mara Cenerenti, Georg Alexander Rockinger, Tania Wyss, Philippe Guillaume, Julien Schmidt, Raphael Genolet, Giuseppe Ercolano, Maria Pia Protti, Walter Reith, Kalliopi Ioannidou, Laurence de Leval, Joseph A. Trapani, George Coukos, Alexandre Harari, Daniel E. Speiser, Alexander Mathis, David Gfeller, Hatice Altug, Pedro Romero, Camilla Jandus
Summary: CD4 T cells displaying cytotoxic phenotypes were identified in different human cancers through mining single-cell RNA-seq datasets. Ex vivo confirmation of the cytolytic tumor-specific CD4 T cells was achieved using peptide-MHCII-multimer technology. The cytotoxic activity of these cells, partially dependent on SLAMF7, was demonstrated to have delayed kinetics compared to classical cytotoxic lymphocytes, and agonistic engagement of SLAMF7 enhanced their cytotoxicity, indicating potential synergy with other cancer immunotherapies.
Article
Medicine, Research & Experimental
Osaretin E. Asowata, Alveera Singh, Abigail Ngoepe, Nicholas Herbert, Rabiah Fardoos, Kavidha Reddy, Yenzekile Zungu, Faith Nene, Ntombifuthi Mthabela, Dirhona Ramjit, Farina Karim, Katya Govender, Thumbi Ndung'u, J. Zachary Porterfield, John H. Adamson, Fusi G. Madela, Vukani T. Manzini, Frank Anderson, Alasdair Leslie, Henrik N. Kloverpris
Summary: Research conducted on a large cohort recruited from high HIV endemic areas in South Africa revealed that people living with HIV presented at a younger age for GI clinic investigation, with severe CD4(+) T cell depletion in the GI tract, particularly in the colon. Despite full suppression of plasma viremia, HIV-p24 staining showed persistent viral expression, emphasizing the irreversible loss of GI CD4(+) T cells as a key event in HIV pathogenesis in PLWH in South Africa.
Article
Immunology
Marta Calvet-Mirabent, Daniel T. Claiborne, Maud Deruaz, Serah Tanno, Carla Serra, Cristina Delgado-Arevalo, Ildefonso Sanchez-Cerrillo, Ignacio de Los Santos, Jesus Sanz, Lucio Garcia-Fraile, Francisco Sanchez-Madrid, Arantzazu Alfranca, Maria Angeles Munoz-Fernandez, Todd M. Allen, Maria J. Buzon, Alejandro Balazs, Vladimir Vrbanac, Enrique Martin-Gayo
Summary: The combination of 2‘3’-c ' diAM(PS)2 and Poly I:C as adjuvants can enhance DCs' ability to induce polyfunctional HIV-1 specific CD8(+) T-cell responses, reducing the severity of CD4(+) T-cell depletion following HIV-1 infection, and preserving the specific polyfunctional responses of CD8(+) T cells. The priming of DCs with PolyI:C and STING agonists may be useful for future HIV-1 vaccine studies.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Sara Bolivar-Wagers, Jemma H. Larson, Sujeong Jin, Bruce R. Blazar
Summary: Treg cells play a critical role in maintaining immune homeostasis and tolerance induction; however, the mechanisms responsible for their cytotoxicity and therapeutic potential have not been fully explored.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Caroline Dufour, Corentin Richard, Marion Pardons, Marta Massanella, Antoine Ackaoui, Ben Murrell, Bertrand Routy, Rejean Thomas, Jean-Pierre Routy, Remi Fromentin, Nicolas Chomont
Summary: The phenotypic diversity of HIV-infected cells persisting during antiretroviral therapies (ART) was investigated. CD4+ T cells expressing integrin VLA-4 were found to be enriched in replication-competent HIV. Clonally expanded cells with identical proviruses displayed diverse phenotypes, indicating the role of cellular proliferation in the phenotypic diversification of the HIV reservoir. Genetically intact and inducible viral genomes were associated with higher levels of VLA-4 expression in CD4+ T cells. Replication-competent HIV was highly enriched in memory CD4+ T cells expressing high levels of VLA-4.
NATURE COMMUNICATIONS
(2023)
Article
Geriatrics & Gerontology
Claudia M. Trujillo-Vargas, Kelsey E. Mauk, Humberto Hernandez, Rodrigo G. de Souza, Zhiyuan Yu, Jeremias G. Galletti, Jana Dietrich, Friedrich Paulsen, Cintia S. de Paiva
Summary: Aging is associated with infiltration of T lymphocytes in the lacrimal gland. Our study found differences in the immune phenotype of aged CD4(+) T cells between the lacrimal gland and lymphoid organs. Aged Tregs showed upregulation of Th1 genes, while non-Tregs cells exhibited increased levels associated with cell exhaustion, immunopathology, and the generation of tertiary lymphoid tissue.
Article
Medicine, General & Internal
Elsa Brunet-Ratnasingham, Antigoni Morou, Mathieu Dube, Julia Niessl, Amy E. Baxter, Olivier Tastet, Nathalie Brassard, Gloria Ortega-Delgado, Roxanne Charlebois, Gordon J. Freeman, Cecile Tremblay, Jean-Pierre Routy, Daniel E. Kaufmann
Summary: This study examined the expression and function of immune checkpoints in CD4+ T cells of HIV-infected individuals and found that the expression of immune checkpoints is associated with infection status and effector profile. In addition, different subsets of CD4+ T cells show varying sensitivity to PD-1-mediated inhibition, suggesting heterogeneity in the restoration of cell function through immune checkpoint blockade.
Article
Biochemistry & Molecular Biology
John T. T. Bates
Summary: This study investigated the activation of naïve CD4(+) T cells in the nasal-associated lymphoid tissues (NALT). The results showed that antigen can be transported from the airway lumen to the interior of the NALT through transepithelial transport. Antigen-specific CD4(+) T cells in the NALT formed clusters after immunization, while control mice immunized with adjuvant only had dispersed CD4(+) T cells. The populations of antigen-specific CD4(+) T cells in the NALT and cranial deep cervical lymph nodes significantly expanded three days after immunization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Quentin Le Hingrat, Irini Sereti, Alan L. Landay, Ivona Pandrea, Cristian Apetrei
Summary: CD4(+) T-cell depletion is a key feature of AIDS in both HIV and SIV infections, occurring early and being most significant at mucosal sites. The clinical outcome is associated with mucosal CD4(+) T-cell recovery during chronic infection, while immune activation and inflammation play critical roles in CD4(+) T-cell depletion.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Xiao-Peng Dai, Feng-Ying Wu, Cheng Cui, Xue-Jiao Liao, Yan-Mei Jiao, Chao Zhang, Jin-Wen Song, Xing Fan, Ji-Yuan Zhang, Qing He, Fu-Sheng Wang
Summary: Platelet-T cell aggregates play a critical role in maintaining inflammation in chronic HIV-1 infection. The formation of platelet-CD4(+) T cell aggregates was increased in treatment-naive HIV-1-infected individuals compared to healthy controls. Higher levels of these aggregates were associated with HIV-1 permissiveness and immune activation during HIV-1 infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Tanner F. Robertson, Yiran Hou, Jonathan Schrope, Simone Shen, Julie Rindy, John-Demian Sauer, Huy Q. Dinh, Anna Huttenlocher
Summary: In this study, transparent zebrafish were used to investigate how T cells organize and survey for antigen in the absence of lymph nodes. It was found that naive-like T cells in zebrafish form a previously unknown whole-body lymphoid network that facilitates collective migration and coordinated trafficking. During infection, T cells switch from collective migration to individual random walks to prioritize antigen search.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Eirini Moysi, Perla M. Del Rio Estrada, Fernanda Torres-Ruiz, Gustavo Reyes-Teran, Richard A. Koup, Constantinos Petrovas
Summary: CD4 T cells play a key role in adaptive immune responses during infections and vaccinations, with Tfh cells providing critical help to B-cells and contributing to HIV reservoir maintenance. Understanding the tissue-specific microenvironment and immune cell subsets that affect Tfh cell differentiation is important for designing effective prevention and cure strategies. The application of multispectral confocal microscopy and immunofluorescence panels offers a comprehensive approach for analyzing immune cell targets in lymphoid tissues.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Darya Malko, Tarek Elmzzahi, Marc Beyer
Summary: Treg cells play a crucial role in controlling autoimmunity, immune responses during infections and tumor development, and tissue homeostasis. This review highlights the recent findings on the differentiation and function of tissue Treg cells, emphasizing their importance in tissue maintenance, regeneration, and repair in various organs.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Constance Renault, Nicolas Veyrenche, Franck Mennechet, Anne-Sophie Bedin, Jean-Pierre Routy, Philippe Van de Perre, Jacques Reynes, Edouard Tuaillon
Summary: Th17 cells play a crucial role in defending against pathogens at mucosal barriers, but they are also vulnerable to HIV-1 infection and depletion from gut mucosal sites. The imbalance caused by the loss of Th17 cells impairs cytokine production and leads to damage in the gut mucosal barrier, promoting HIV-1 disease progression. The expression of specific receptors by Th17 cells contributes to their susceptibility to HIV infection. Moreover, Th17 cells serve as long-lived viral reservoirs in HIV patients receiving antiretroviral therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Donna L. Farber, Joshua I. Gray
Summary: Susceptibility to respiratory pathogens is increased during early life, yet children can mount highly effective immune responses to novel pathogens in the absence of a fully developed immune system. We found that bronchus-associated lymphoid tissue (BALT) develops in the lungs early in life and supports germinal center formation and B cell differentiation to produce antibodies specific for respiratory pathogens, revealing a mechanism for immune protection in an as-yet-undeveloped immune system.
Article
Immunology
Hannes Lindahl, Puran Chen, Mikael Aberg, Hans-Gustaf Ljunggren, Marcus Buggert, Soo Aleman, C. I. Edvard Smith, Peter Bergman
Summary: This study investigated the cross-reactivity between vaccine-induced anti-SARS-CoV-2 antibodies and different viral variants. The results showed that commercial immunoglobulin batches currently contain large quantities of vaccine-induced antibodies, with evident but varying cross-reactivity towards variant strains, particularly low neutralizing potential against Omicron variants.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Editorial Material
Immunology
Marcus Buggert
Summary: The oral mucosa plays a crucial role in defending against infections. Stolley et al. discovered that resident memory T cells, specifically CD8(+) CD103(+) cells, in the oral mucosa are vital for protecting against local viral infections in mice.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Immunology
Yichao Zheng, Fei Han, Amanda Ho, Yiting Xue, Zhengyu Wu, Xingchi Chen, Johan K. Sandberg, Shaohua Ma, Edwin Leeansyah
Summary: Mucosa-associated invariant T (MAIT) cells are a major population of unconventional T cells in humans. They have rapid effector responses and can recognize microbial riboflavin-like antigens. The presentation of these unique small molecule metabolite antigens is mediated by a highly conserved protein. The role of MAIT cells in gastrointestinal bacterial infections varies depending on the etiological agents and anatomical location.
MUCOSAL IMMUNOLOGY
(2023)
Review
Immunology
Marcus Buggert, David A. Price, Laura K. Mackay, Michael R. Betts
Summary: Our current understanding of human memory CD8(+) T cells mainly comes from studies of the intravascular space, but new data challenges some established ideas and suggests the need for conceptual revision. This review provides a brief history of the field and summarizes the biology of circulating and tissue-resident memory CD8(+) T cells, which play a crucial role in immune surveillance. The authors also discuss how future human studies can improve our understanding of CD8(+) T cells and inform the development of better immunotherapies and vaccines.
Review
Microbiology
Raphael J. Landovitz, Hyman Scott, Steven G. Deeks
Summary: In this Review, the authors explore the current state of HIV prevention and treatment, highlighting unmet needs and emerging tools. They discuss the combination of different approaches to achieve better outcomes, and describe recent progress in pre-exposure prophylaxis, vaccines, treatment, and cure. They emphasize the need for continued efforts to develop effective preventative vaccines and scalable cures, as the limitations of antiretroviral drugs become more apparent.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Microbiology
LaTonya Williams, Xiaoying S. Shen, Sheetal Sawant, Siriwat C. Akapirat, Lindsay Dahora, Matthew Zirui Tay, Sherry Stanfield-Oakley, Saintedym Wills, Derrick Goodman, DeAnna Tenney, Rachel L. Spreng, Lu Zhang, Nicole L. Yates, David C. Montefiori, Michael A. Eller, David Easterhoff, Thomas J. Hope, Supachai Rerks-Ngarm, Punnee Pittisuttithum, Sorachai Nitayaphan, Jean-Louis Excler, Jerome H. Kim, Nelson L. Michael, Merlin L. Robb, Robert J. O'Connell, Nicos Karasavvas, Sandhya Vasan, Guido Ferrari, Georgia D. Tomaras
Summary: The RV305 HIV-1 clinical trial evaluated the immunological impact of booster immunogens in RV144 recipients after 6-8 years. The study showed that the ALVAC vaccine component directly improved the breadth, function, and durability of vaccine-elicited antibodies. However, the impact of different immunogens on HIV-1 epitope specificity, antibody subclasses, and Fc effector functions is still unknown.
Editorial Material
Immunology
Barbara L. Shacklett, Marcus Buggert, Joana Dias
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Margaret C. Costanzo, Dominic Paquin-Proulx, Alexandra Schuetz, Siriwat Akapirat, Zhanna Shubin, Dohoon Kim, Lindsay Wieczorek, Victoria R. Polonis, Hung V. Trinh, Mangala Rao, Hanna Anenia, Michael D. Barrera, Jacob Boeckelman, Barbara Nails, Pallavi Thapa, Michelle Zemil, Carlo Sacdalan, Eugene Kroon, Boot Kaewboon, Somporn Tipsuk, Surat Jongrakthaitae, Sanjay Gurunathan, Faruk Sinangil, Jerome H. Kim, Merlin L. Robb, Julie A. Ake, Robert J. O'Connell, Punnee Pitisutthithum, Sorachai Nitayaphan, Suwat Chariyalertsak, Michael A. Eller, Nittaya Phanuphak, Sandhya Vasan
Summary: The combination of ALVAC-HIV with AIDSVAX B/E significantly enhances cellular and humoral immune responses compared to the administration of AIDSVAX B/E alone, leading to increased efficacy in preventing HIV acquisition. This is evidenced by increased CD4+ HIV-specific T cell responses, polyfunctionality, and proliferation, as well as the identification of Env-specific plasmablasts and A244-specific memory B cells in the ALVAC-HIV group. Furthermore, plasma IgG binding to and avidity for HIV Env, as well as Fc-mediated effector functions, including antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis, were significantly higher in participants who received ALVAC-HIV.
Correction
Immunology
Marcus Buggert, David A. Price, Laura K. Mackay, Michael R. Betts
Correction
Immunology
Amy D. Proal, Michael B. VanElzakker, Soo Aleman, Katie Bach, Brittany P. Boribong, Marcus Buggert, Sara Cherry, Daniel S. Chertow, Helen E. Davies, Christopher L. Dupont, Steven G. Deeks, William Eimer, E. Wesley Ely, Alessio Fasano, Marcelo Freire, Linda N. Geng, Diane E. Griffin, Timothy J. Henrich, Akiko Iwasaki, David Izquierdo-Garcia, Michela Locci, Saurabh Mehandru, Mark M. Painter, Michael J. Peluso, Etheresia Pretorius, David A. Price, David Putrino, Richard H. Scheuermann, Gene S. Tan, Rudolph E. Tanzi, Henry F. Vanbrocklin, Lael M. Yonker, E. John Wherry
Review
Immunology
Amy D. Proal, Michael B. VanElzakker, Soo Aleman, Katie Bach, Brittany P. Boribong, Marcus Buggert, Sara Cherry, Daniel S. Chertow, Helen E. Davies, Christopher L. Dupont, Steven G. Deeks, William Eimer, E. Wesley Ely, Alessio Fasano, Marcelo Freire, Linda N. Geng, Diane E. Griffin, Timothy J. Henrich, Akiko Iwasaki, David Izquierdo-Garcia, Michela Locci, Saurabh Mehandru, Mark M. Painter, Michael J. Peluso, Etheresia Pretorius, David A. Price, David Putrino, Richard H. Scheuermann, Gene S. Tan, Rudolph E. Tanzi, Henry F. VanBrocklin, Lael M. Yonker, E. John Wherry
Article
Cell Biology
Thomas R. R. Muller, Takuya Sekine, Darya Trubach, Julia Niessl, Puran Chen, Peter Bergman, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Jan Vesterbacka, Mira Akber, Anna Olofsson, Susana Patricia Amaya Hernandez, Yu Gao, Curtis Cai, Gunnar Soderdahl, C. I. Edvard Smith, Anders Osterborg, Karin Lore, Margaret Sallberg Chen, Per Ljungman, Hans-Gustaf Ljunggren, Annika C. C. Karlsson, Sunil Kumar Saini, Soo Aleman, Marcus Buggert
Summary: Suboptimal immunity to SARS-CoV-2 mRNA vaccination is common in immunodeficient individuals. T cell responses were assessed in 279 individuals with different immunodeficiencies and healthy controls before and after booster vaccination, as well as after Omicron infection. Robust and persistent Omicron-reactive T cell responses were observed, which increased significantly after booster vaccination and correlated with antibody titers in all patient groups. Additional vaccine doses effectively countered poor vaccination responsiveness in immunocompromised or elderly individuals.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Massimiliano Bissa, Veronica Galli, Luca Schifanella, Monica Vaccari, Mohammad Arif Rahman, Giacomo Gorini, Nicolo Binello, Sarkis Sarkis, Anna Gutowska, Isabela Silva de Castro, Melvin N. Doster, Ramona Moles, Guido Ferrari, Xiaoying Shen, Georgia D. Tomaras, David C. Montefiori, Kombo F. N'guessan, Dominic Paquin-Proulx, Pamela A. Kozlowski, David J. Venzon, Hyoyoung Choo-Wosoba, Matthew W. Breed, Joshua Kramer, Genoveffa Franchini
Summary: The efficacy of the DNA/ALVAC/gp120/alum vaccine in the absence of neutralizing antibodies is attributed to a delicate balance of pro-and anti-inflammatory immune responses, which effectively reduces the risk of SIVmac251 acquisition in macaques. This efficacy is associated with antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells promoting the clearance of apoptotic cells through efferocytosis, and downregulation of CCR5 on vaccine-induced gut homing CD4(+) cells. IGF-1, a potent RAS activator, was found to alter epitope recognition and affect ADCC and efferocytosis, but it also compensates for these negative effects by reducing CCR5 expression on CD4(+) gut-homing T-cells, resulting in equivalent vaccine efficacy (71% with IGF-1 and 69% without).
Article
Multidisciplinary Sciences
Viviana Cobos Jimenez, Aviva Geretz, Andrey Tokarev, Philip K. Ehrenberg, Selase Deletsu, Kawthar Machmach, Prakriti Mudvari, J. Natalie Howard, Amanda Zelkoski, Dominic Paquin-Proulx, Gregory Q. Del Prete, Caroline Subra, Eli A. Boritz, Alberto Bosque, Rasmi Thomas, Diane L. Bolton
Summary: AP-1 transcription factor plays an important role in latent HIV-1 infection and reactivation. Inhibiting AP-1 may be a potential therapeutic approach to limit HIV-1 reservoirs.
Article
Respiratory System
Laura Palma M. Medina, Haris Babacic, Majda Dzidic, Asa Parke, Marina Garcia, Kimia T. Maleki, Christian Unge, Magda Lourda, Egle Kvedaraite, Puran Chen, Jagadeeswara Rao Muvva, Martin Cornillet, Johanna Emgard, Kirsten Moll, Jakob Michaelsson, Malin Flodstrom-Tullberg, Susanna Brighenti, Marcus Buggert, Jenny Mjosberg, Karl-Johan K. Malmberg, Johan Sandberg, Sara Gredmark-Russ, Olav Rooyackers, Mattias J. Svensson, Benedict I. Chambers, Lars Eriksson, Maria K. Pernemalm, Niklas Bjorkstrom, Soo Aleman, Hans-Gustaf Ljunggren, Jonas Klingstrom, Kristoffer Stralin, Anna Norrby-Teglund
Summary: This study explores the plasma proteome profiles in COVID-19 and sepsis patients, revealing similarities and specific differences. Machine learning identifies biomarkers that accurately differentiate COVID-19 from CAP-sepsis, which has significant implications for personalized management of these diseases.
RESPIRATORY RESEARCH
(2023)