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Cells
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Immune Response in Transplantation
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Immune Response in Transplantation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 5473

Special Issue Editors

Dr. Susan E. Prockop

E-Mail Website
Guest Editor
1. Stem Cell Transplant Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA
2. Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA, USA
Interests: hematopoietic stem cell transplant; immune reconstitution; opportunistic infection
Dr. Tanvi Sharma

E-Mail Website
Guest Editor
Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA
Interests: hematopoietic stem cell transplant; immune reconstitution; opportunistic infection

Special Issue Information

Dear Colleagues,

Allogeneic hematopoietic stem cell transplant (HCT) is followed by a period of profound immune compromise with defects in both innate and adaptive immunity. Critical to successful HCT is re-establishing both arms of immunity with innate immunity typically being restored in the first month or so after HCT.   The reconstitution of T cell immunity occurs more slowly by both homeostatic expansion of populations infused at the time of transplant as well as by de novo thymic dependent T cell production. For over two decades we have understood that the pace of these processes contributes to transplant outcomes including relapse and non-relapse mortality and is controlled by both modifiable and non-modifiable variables. This issue will explore recent advances in measuring as well as modifying the process of immune reconstitution and link these advances to the infectious complications associated with defects in immunity seen after HCT.

We propose a special issue focused on the interaction in the post-hematopoietic stem cell transplant period between components of immune reconstitution and infectious complications. We would solicit manuscripts on reconstitution of innate and adaptive immunity, manuscripts on specific infectious risks related to defects in each of these components of protective immunity, and a position paper on identifying high risk patients and approaches to monitoring in these patients, as well as what the future looks like in this arena.

Dr. Susan E. Prockop
Dr. Tanvi Sharma
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hematopoietic stem cell transplant
  • immune reconstitution
  • opportunistic infection

Published Papers (3 papers)

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Research

12 pages, 974 KiB  
Article
Generation of Human Regulatory Dendritic Cells from Cryopreserved Healthy Donor Cells and Hematopoietic Stem Cell Transplant Recipients
by Sabrina M. Scroggins and Annette J. Schlueter
Cells 2023, 12(19), 2372; https://doi.org/10.3390/cells12192372 - 28 Sep 2023
Viewed by 933
Abstract
Acute graft versus host disease (GVHD) remains a significant complication following hematopoietic stem cell transplant (HSCT), despite improved human leukocyte antigen (HLA) matching and advances in prophylactic treatment regimens. Previous studies have shown promising results for future regulatory dendritic cell (DCreg) therapies in [...] Read more.
Acute graft versus host disease (GVHD) remains a significant complication following hematopoietic stem cell transplant (HSCT), despite improved human leukocyte antigen (HLA) matching and advances in prophylactic treatment regimens. Previous studies have shown promising results for future regulatory dendritic cell (DCreg) therapies in the amelioration of GVHD. This study evaluates the effects of cryopreservation on the generation of DCreg, the generation of young and older DCreg in serum-free media, and the feasibility of generating DCreg from young and older HSCT patient monocytes. DCregs were generated in X-vivo 15 serum-free media from donor or patient monocytes. This study includes the use of monocytes from young and older healthy, donor, and HSCT patients with varying hematological diseases. Phenotypic differences in cell populations were assessed via flow cytometry while pro-inflammatory and anti-inflammatory cytokine production was evaluated in culture medium. The number of DCreg generated from cryopreserved monocytes of healthy donors was not significantly different from freshly isolated monocytes. DCreg generated from cryopreserved monocytes had comparable levels of co-stimulatory molecule expression, inhibitory molecule expression, and cytokine production as freshly isolated monocytes. Young and older healthy donor monocytes generated similar numbers of DCreg with similar cytokine production and phenotype. Although monocytes from older HSCT patients generated significantly fewer DCreg, DCreg from young and older HSCT patients had comparable phenotypes and cytokine production. Monocytes from young and older myelodysplastic syndrome (MDS) patients generated reduced numbers of DCreg compared to non-MDS-derived DCreg. We demonstrate that the cryopreservation of monocytes from HSCT patients of varying hematological diseases allows for the cost-effective generation of DCreg on an as-needed basis. Although the generation of DCreg from MDS patients requires further assessment, these data support the possibility of in vitro-generated DCreg as a therapy to reduce GVHD-associated morbidity and mortality in young and older HSCT recipients. Full article
(This article belongs to the Special Issue Immune Response in Transplantation)
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16 pages, 3875 KiB  
Article
Autoimmune Limbic Encephalitis in Patients with Hematologic Malignancies after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide
by Bu Yeon Heo, Myung-Won Lee, Suyoung Choi, Yunju Jung, Thi Thuy Duong Pham, Yunseon Jang, Jung-Hyun Park, Sora Kang, Jeong Suk Koh, Deog-Yeon Jo, Jaeyul Kwon and Ik-Chan Song
Cells 2023, 12(16), 2049; https://doi.org/10.3390/cells12162049 - 11 Aug 2023
Cited by 1 | Viewed by 1708
Abstract
Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and [...] Read more.
Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflammatory biomarkers, and reconstitution of various T cell populations. Of 35 patients, 4 developed LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies. Full article
(This article belongs to the Special Issue Immune Response in Transplantation)
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20 pages, 2208 KiB  
Article
Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes
by Dragan Copic, Martin Direder, Katharina Klas, Daniel Bormann, Maria Laggner, Hendrik Jan Ankersmit and Michael Mildner
Cells 2023, 12(3), 382; https://doi.org/10.3390/cells12030382 - 20 Jan 2023
Cited by 2 | Viewed by 2388
Abstract
Background: Antithymocyte globulins (ATG) are T cell-depleting antibodies used in solid organ transplantation for induction therapy in sensitized patients with a high risk of graft rejection. Previously described effects besides the depletion of T cells have suggested additional modes of action and identified [...] Read more.
Background: Antithymocyte globulins (ATG) are T cell-depleting antibodies used in solid organ transplantation for induction therapy in sensitized patients with a high risk of graft rejection. Previously described effects besides the depletion of T cells have suggested additional modes of action and identified further cellular targets. Methods: We examined the transcriptional changes arising in immune cells from human blood after ex vivo stimulation with ATG at the single-cell level to uncover additional mechanisms by which ATG regulates T cell activity and effector functions. Findings: Analysis of the paracrine factors present in the plasma of ATG-treated whole blood revealed high levels of chemokines and cytokines, including interferon-γ (IFN-γ). Furthermore, we identified an increase in the surface expression of the programmed death ligand 1 (PDL-1) on monocytes mediated by the released paracrine factors. In addition, we showed that this induction is dependent on the activation of JAK/STAT signaling via the binding of IFN-γ to interferon-γ receptor 1 (IFN-γR1). Lastly, we demonstrated that the modulation of the immune regulatory axis of programmed cell death protein 1 (PD1) on activated CD8+ T cells with PDL-1 found on monocytes mediated by ATG potently inhibits effector functions including the proliferation and granzyme B release of activated T cells. Interpretation: Together, our findings represent a novel mode of action by which ATG exerts its immunosuppressive effects. Full article
(This article belongs to the Special Issue Immune Response in Transplantation)
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