B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated by B cell APCs. This finding led us to identify a process in mice whereby Ag-specific B cells transfer Ag to other APCs. In this study, we report the ability and mechanism by which human B lymphocytes can transfer BCR-captured Ag to macrophages. The transfer of Ag involves direct contact between the two cells followed by the capture of B cell-derived membrane and/or intracellular components by the macrophage. These events are abrogated by blocking scavenger receptor A, a receptor involved in the exchange of membrane between APCs. Macrophages acquire greater amounts of Ag in the presence of specific B cells than in their absence. This mechanism allows B cells to amplify or edit the immune response to specific Ag by transferring BCR-captured Ag to other professional APCs, thereby increasing the frequency of its presentation. Ag transfer may perpetuate chronic autoimmune responses to specific self-proteins and help explain the efficacy of B cell-directed therapies in human disease.
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http://dx.doi.org/10.4049/jimmunol.181.6.4043 | DOI Listing |
Oncotarget
January 2025
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Recently, combination checkpoint therapy of cancer has been recognized as producing additive as opposed to synergistic benefit due in part to positively correlated effects. The potential for uncorrelated or negatively correlated therapies to produce true synergistic benefits has been noted. Whereas the inhibitory receptors PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT have been collectively characterized as exhaustion receptors, another inhibitory receptor KLRG1 was historically characterized as a senescent receptor and received relatively little attention as a potential checkpoint inhibitor target.
View Article and Find Full Text PDFJ Infect Dev Ctries
December 2024
Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
Co-inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), known as immune checkpoints, regulate the activity of T and myeloid cells during chronic viral infections and are well-established for their roles in cancer therapy. However, their involvement in chronic bacterial infections, particularly those caused by pathogens endemic to developing countries, such as Mycobacterium tuberculosis (Mtb), remains incompletely understood. Cytokine microenvironment determines the expression of co-inhibitory molecules in tuberculosis: Results indicate that the cytokine IL-12, in the presence of Mtb antigens, can enhance the expression of co-inhibitory molecules while preserving the effector and memory phenotypes of CD4+ T cells.
View Article and Find Full Text PDFOncologist
January 2025
Department of Medical Oncology, Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada.
Background: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis, necessitating the investigation of novel treatments and targets. This study evaluated JNJ-70218902 (JNJ-902), a T-cell redirector targeting transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2) and cluster of differentiation 3, in mCRPC.
Patients And Methods: Patients who had measurable/evaluable mCRPC after at least one novel androgen receptor-targeted therapy or chemotherapy were eligible.
Immunol Res
January 2025
Immunology Laboratory, Department of Physiology, University Colleges of Science and Technology, University of Calcutta, 92 APC Road, Calcutta, 700009, West Bengal, India.
Septic arthritis (SA) caused by Staphylococcus aureus is a severe inflammatory joint disease, characterized by synovitis accompanied with cartilage destruction and bone erosion. The available antibiotic treatment alone is insufficient to resolve the inflammation that leads to high rates of morbidity and mortality. Among the CD4 T helper lymphocytes, the Th17 and Tregs are key regulators of immune homeostasis.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Program of Cell and Gene Therapy, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil.
Antigen recognition by CD8+ T-cell receptors (TCR) is crucial for immune responses to pathogens and tumors. TCRs are cross-reactive, a single TCR can recognize multiple peptide-Human Leukocyte Antigen (HLA) complexes. The study of cross-reactivity can support the development of therapies focusing on immune modulation, such as the expansion of pre-existing T-cell clones to fight pathogens and tumors.
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