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Under steady-state conditions, conventional CD4+ T lymphocytes are classically divided into naïve (CD44lo CD62Lhi) and memory (CD44hi CD62Llo) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific "authentic" memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4+ T lymphocytes are divided into CD127hi Sca1lo, CD127hi Sca1hi, CD127lo Sca1hi, and CD127lo Sca1lo subpopulations that are Bcl2lo, while foreign Ag-specific memory cells are CD127hi Sca1hi Bcl2hi. We further show that among the four MP subsets, CD127hi Sca1hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4+ T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127hi Sca1hi MP cells. [ABSTRACT FROM AUTHOR]

Objective: CD204+ tumor‐associated macrophages are associated with adverse outcomes of various malignancies. We performed a study to elucidate the role of CD204+ macrophages in allogeneic hematopoietic cell transplantation (allogeneic HCT). Methods: In a total of 81 patients who received allogeneic HCT for non‐remission malignant lymphoma, immunohistochemical staining of CD204 using specimens preserved before allogeneic HCT was performed. According to the average number of CD204+ macrophages in a high‐power field, patients were categorized into three groups: low (<25th percentile), intermediate (≥25th percentile and <50th percentile), and high (≥50th percentile). Results: The B‐cell lymphoma proportion was higher in the low group, while T‐cell lymphoma and adult T‐cell leukemia proportions were higher in the high group. The 3‐year overall survival (OS) was poorest in the high group; low vs intermediate vs high = 83.3% vs 43.7% vs 20.2% (P < .01). The 3‐year cumulative incidences of relapse were significantly higher in the high group than the intermediate and low groups: 67.0% vs 38.1% vs 18.2% (P < .01). In multivariate analyses, the numbers of CD204+ macrophages were independent risk factors of poorer OS and cumulative incidences of relapse. Conclusions: CD204+ macrophages might be associated with poorer prognosis in allogeneic HCT for malignant lymphomas. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Nodal Epstein-Barr virus-positive T/NK-cell lymphoma (EB-nTNKL) is an extremely rare disease characterized by an aggressive clinical course and poor prognosis, for which treatment strategies have not yet been established. We herein report a young man with EB-nTNKL. Although initial chemotherapies, including L-asparaginase, failed to produce a good response, subsequent myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT) resulted in favorable disease control and a long-term disease-free survival. The prompt performance of alloHSCT using an available donor source at that time, regardless of whether or not the initial chemotherapy was effective, could be critical to saving patients with this otherwise fatal disease.

A 21-year-old man was diagnosed with myeloid/natural killer precursor leukemia (MNKPL) with bone marrow infiltration of blasts of cyCD3 + , CD7 + , CD33 + , CD34 dim , CD56 +/- , HLA-DR + , cyMPO + , and TdT - immunophenotypes. Although hyper-CVAD therapy was unsuccessful, induction treatment with idarubicin and cytarabine resulted in complete remission (CR). The patient subsequently underwent cord blood transplantation with a myeloablative conditioning regimen, which resulted in durable CR and complete donor chimerism. He had been in good health without relapse for over nine months since transplantation. Timely allogeneic hematopoietic stem cell transplantation using an available donor source may be a promising treatment strategy for MNKPL.

Conventional CD4 + T lymphocytes consist of naïve, foreign antigen-specific memory, and self-antigen-driven memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells tonically proliferate in response to self-antigens and differentiate into the T-bet + subset in steady state. How excess proliferation and differentiation of MP cells are inhibited remains unclear. Given immunosuppressive function of regulatory T cells (Tregs), it is possible that they are also involved in inhibition of spontaneous MP cell activation. Here we show using Foxp3-diphtheria toxin receptor-transgenic mice that both MP and naïve CD4 + T cells spontaneously proliferate and differentiate into Th1 cells upon acute Treg depletion. At an early time point post Treg depletion, MP as compared to naïve CD4 + T cells are preferentially activated while at a later stage, the response is dominated by activated cells originated from the naïve pool. Moreover, we argue that MP cell proliferation is driven by TCR and CD28 signaling whereas Th1 differentiation mediated by IL-2. Furthermore, our data indicate that such activation of MP and naïve CD4 + T lymphocytes contribute to development of multi-organ inflammation at early and later time points, respectively, after Treg ablation. Together our findings reveal that Tregs tonically inhibit early, spontaneous proliferation and Th1 differentiation of MP CD4 + T lymphocytes as well as late activation of naïve cells, thereby contributing to maintenance of T cell homeostasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Li, Yang, Kawajiri, Sato, Tayama, Ishii, Zhu and Kawabe.)

Group 2 innate lymphoid cells (ILC2s) are resident cells and participate in innate and adaptive immunity. In the tumor microenvironment (TME), ILC2s contribute to both tumorigenesis and inhibition of tumor growth, but the true role of ILC2s in TME construction remains unclear. We show that IL-33 treatment induces an anti-tumor effect in vivo in a mouse model of melanoma in which ILC2s and CD8 + T cells infiltrate into tumor tissue. This anti-tumor effect is dependent on CD8 + T cells, however, IL-33 does not act directly on CD8 + T cells because the cells lack ST2, the receptor for IL-33. ILC2s and CD8 + T cells in tumors of IL-33-treated mice express OX40 ligand (OX40L) and OX40, respectively, and in vivo blockade of OX40L-OX40 interaction canceled the anti-tumor effect of IL-33. Co-culture of CD8 + T cells expressing OX40 with IL-33-stimulated ILC2 expressing OX40L promoted cell activation and proliferation of CD8 + T cells, which was significantly suppressed by administration of anti-OX40L blocking antibody. Thus, the IL-33-ILC2 axis promotes CD8 + T cell responses via OX40/OX40L interaction and exerts an anti-tumor effect., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Naoto Ishii reports financial support was provided by Tohoku University Graduate School of Medicine. Naoto Ishii reports financial support was provided by Japan Society for the Promotion of Science., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Under steady-state conditions, conventional CD4 + T lymphocytes are classically divided into naïve (CD44 lo CD62L hi ) and memory (CD44 hi CD62L lo ) cell compartments. While the latter population is presumed to comprise a mixture of distinct subpopulations of explicit foreign antigen (Ag)-specific "authentic" memory and foreign Ag-independent memory-phenotype (MP) cells, phenotypic markers differentially expressed in these two cell types have yet to be identified. Moreover, while MP cells themselves have been previously described as heterogeneous, it is unknown whether they consist of distinct subsets defined by marker expression. In this study, we demonstrate using combined single-cell RNA sequencing and flow cytometric approaches that self-driven MP CD4 + T lymphocytes are divided into CD127 hi Sca1 lo , CD127 hi Sca1 hi , CD127 lo Sca1 hi , and CD127 lo Sca1 lo subpopulations that are Bcl2 lo , while foreign Ag-specific memory cells are CD127 hi Sca1 hi Bcl2 hi . We further show that among the four MP subsets, CD127 hi Sca1 hi lymphocytes represent the most mature and cell division-experienced subpopulation derived from peripheral naïve precursors. Finally, we provide evidence arguing that this MP subpopulation exerts the highest responsiveness to Th1-differentiating cytokines and can induce colitis. Together, our findings define MP CD4 + T lymphocytes as a unique, self-driven population consisting of distinct subsets that differ from conventional foreign Ag-specific memory cells in marker expression and establish functional relevance for the mature subset of CD127 hi Sca1 hi MP cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kawabe, Ciucci, Kim, Tayama, Kawajiri, Suzuki, Tanaka, Ishii, Jankovic, Zhu, Sprent, Bosselut and Sher.)

Primary graft failure is a lethal complication that occurs after allogeneic stem cell transplantation (allo-SCT) and requires retransplantation. We retrospectively assessed 1,355 patients who underwent allo-SCT at our institute. Following allo-SCT, the cumulative incidence of subsequent neutrophil engraftment was calculated each day after day 5 among patients with white blood cell (WBC) count<100 cells/μL on the respective day. The number of patients with WBC count<100 cells/μL at days 14, 21, and 28 were 372, 55, and 21, respectively. In patients with WBC count<100 cells/μL on day 14, the cumulative incidence of engraftment was lower in recipients of peripheral blood stem cells (PBSCs) and cord blood (CB) compared with recipients of bone marrow (BM) (BM vs. PBSCs vs. CB, 93% vs. 79% vs. 77%, P <0.01). In patients with WBC count<100 cells/μL after day 14, the cumulative incidence of engraftment in recipients of PBSCs became progressively lower (25% at day 21 and 0% at day 28). In patients with WBC count<100 cells/μL on day 28, the cumulative incidence of engraftment was 100% in patients with donor chimerism≥95%, while it was only 13% in those with chimerism<95% ( P <0.01). These data provide important information that could be useful in deciding the appropriate time for performing tests in patients with donor chimerism and in those that require retransplantation., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available here., (Copyright Ⓒ2019 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)