The regeneration of T cell subsets was studied with double immunofluorescence marker methods in 37 patients who received HLA matched T lymphocyte depleted bone marrow transplants (BMT) as part of the treatment for their haematological disease. A cocktail of anti-pan-T (CD6: MBG6) and anti-suppressor/cytotoxic-T cell (CD8: RFT8) monoclonal antibodies was used with rabbit serum as a source of cytolytic complement to achieve selective T cell lysis. The T8+ cells reached low normal values around 60 days post-transplant and remained within the normal range throughout the study (greater than 150 days). This observation is in contrast to our previously published results in patients who, after receiving BMT without efficient T cell depletion, had increased numbers of circulation T8+ cells from 60 days post-transplant. In the present study Leu-7+, RFT8- cells reached normal values rapidly but the reconstitution of T4+ lymphocytes was slow: low normal levels were reached only around day 150 following BMT. The degree of graft-versus-host disease (GVHD) seemed to be related to the number of residual T cells infused: two of the three patients who received the highest numbers of T cells developed Grade II III; otherwise GVHD was minimal. Among the clinical parameters studied cytomegalovirus (CMV) immune status moderately influenced reconstitution: at 55-90 days post-transplant T8+ cells were present at the upper normal levels in seven out of 15 patients receiving BMT from CMV seronegative donors, but in none of the 16 individuals receiving BMT from seropositive donors. CMV related complications were relatively uncommon. Thus the most significant factor in preventing 'T8+ cell overshoot' and T cell imbalance during regeneration appears to be the depletion of T (including T8+) lymphocytes from marrow. The differences of T8+ cell reconstitution in this and previous studies may reflect a different regeneration pattern from T cell precursors as opposed to inoculated mature T cells.
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Sci Transl Med
January 2025
Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P. R. China.
Cancer immunotherapies rely on CD8 cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese-bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I-deficient tumors.
View Article and Find Full Text PDFInt J Nanomedicine
January 2025
School of Basic Medicine, Ningxia Medical University, Yinchuan, People's Republic of China.
Background: Colorectal cancer (CRC) is a highly malignant and aggressive gastrointestinal tumor. Due to its weak immunogenicity and limited immune, cell infiltration lead to ineffective clinical outcomes. Therefore, to improve the current prophylaxis and treatment scheme, offering a favorable strategy efficient against CRC is urgently needed.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China.
Background: Different doses of radiotherapy (RT) exert diverse effects on tumor immunity, although the precise irradiation method remains unknown. This study sought to elucidate the influence of combining different doses of RT with immune checkpoint inhibitors (ICIs) on the infiltration of CD8T cells within tumors, thereby augmenting the anti-tumor response.
Methods: Constructing a mouse model featuring bilateral lung cancer tumors subjected to high and low dose irradiation, the analysis of RNA transcriptome sequencing data and immunohistochemical validation for tumors exposed to various dosages guided the selection of the optimal low-dose irradiation scheme.
Front Immunol
January 2025
Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Human natural killer (NK) cells can be sub-divided into two functional subsets but the clinical significance of these CD56 and CD56 NK cells in anti-tumour immunity remains largely unexplored. We determined the relative abundances of gene signatures for CD56 and CD56 NK cells along with 3 stromal and 18 other immune cell types in the patient tumour transcriptomes from the cancer genome atlas bladder cancer dataset (TCGA-BLCA). Using this computational approach, CD56 NK cells were predicted to be the more abundant tumour-infiltrating NK subset which was also associated with improved patient prognosis.
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