scholarly journals Allogeneic chimerism with low-dose irradiation, antigen presensitization, and costimulator blockade in H-2 mismatched mice

Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 557-564 ◽  
Author(s):  
Peter J. Quesenberry ◽  
Suju Zhong ◽  
Han Wang ◽  
Marc Stewart

Abstract We have previously shown that the keys to high-level nontoxic chimerism in syngeneic models are stem cell toxic, nonmyelotoxic host treatment as provided by 100-cGy whole-body irradiation and relatively high levels of marrow stem cells. This approach was unsuccessful in H-2 mismatched B6.SJL to BALB/c marrow transplants, but with tolerization, stable multilineage chimerism was obtained. Ten million B6.SJL spleen cells were infused intravenously into BALB/c hosts on day −10 and (MR-1) anti-CD40 ligand monoclonal antibody (mAb) injected intraperitoneally at varying levels on days −10, −7, −3, 0, and +3 and the BALB/c mice irradiated (100 cGy) and infused with 40 million B6.SJL/H-2 mismatched marrow cells on day 0. Stable multilineage chimerism at levels between 30% to 40% was achieved in the great majority of mice at 1.6 mg anti-CD40 ligand mAb per injection out to 64 weeks after transplantation, without graft-versus-host disease. The transplanted mice were also tolerant of donor B6.SJL, but not third-party CBA/J skin grafts at 8 to 9 and 39 to 43 weeks after marrow transplantation. These data provide a unique model for obtaining stable partial chimerism in H-2 mismatched mice, which can be applied to various clinical diseases of man such as sickle cell anemia, thalassemia, and autoimmune disorders.

2015 ◽  
Vol 91 (10) ◽  
pp. 795-803 ◽  
Author(s):  
Kyung-Hee Song ◽  
Mi-Hyoung Kim ◽  
Seong-Mook Kang ◽  
Seung-Youn Jung ◽  
Jiyeon Ahn ◽  
...  

2020 ◽  
Vol 9 (3) ◽  
pp. 249-262
Author(s):  
Xiaochang Liu ◽  
Zheng Liu ◽  
Duo Wang ◽  
Yang Han ◽  
Sai Hu ◽  
...  

Abstract Whole-body exposure to low-dose radiation due to diagnostic imaging procedures, occupational hazards and radiation accidents is a source of concern. In this study, we analyzed the effects of single and long-term low-dose irradiation on the immune system. Male Balb/c mice received a single whole-body dose of irradiation (0.01, 0.05, 0.2, 0.5 or 1 Gy). For long-term irradiation, mice were irradiated 10 times (total dose of 0.2, 0.5 or 1 Gy) over a period of 6 weeks. Two days after single or long-term irradiation, the numbers of splenic macrophages, natural killer cells and dendritic cells were reduced, and the spleen organ coefficient was decreased. At 2 Days after long-term low-dose irradiation, the number of white blood cells in the peripheral blood of the mice decreased. Between 7 and 14 Days after long-term low-dose irradiation, the number of immune cells in the thymus and spleen began to increase and then stabilized. Th1/Th2 cytokines and reactive oxygen species-related proteins first decreased and then increased to a plateau. Our results show a significant difference in the effects of single and long-term low-dose irradiation on the immune system.


2008 ◽  
Vol 84 (3) ◽  
pp. 201-210 ◽  
Author(s):  
Ning Wu ◽  
Shun-Zi Jin ◽  
Xue-Na Pan ◽  
Shu-Zheng Liu

Radiology ◽  
1980 ◽  
Vol 134 (2) ◽  
pp. 503-506 ◽  
Author(s):  
J S Melamed ◽  
M G Chen ◽  
J W Brown ◽  
C A Katagiri
Keyword(s):  
Low Dose ◽  

1966 ◽  
Vol 123 (1) ◽  
pp. 103-118 ◽  
Author(s):  
William L. Elkins

The graft versus host reaction (GVHR), which results from the injection of parental strain spleen cells beneath the kidney capsule of F1 hybrid rats, is transferable during its developmental phase into F1 hybrid hosts isogeneic with the primary host, but not into secondary hosts of the parental (donor) strain. Furthermore, the GVHR propagates but rarely in secondary hybrid hosts which are allogeneic with respect to the primary hosts, but which are also genetically tolerant of donor-type cells. These findings indicate that the donor cells not only initiate the GVHR but also maintain it by virtue of immunologically specific activity. Whole-body irradiation of (LBf)F1 and (LBN)F1 hosts 24 hours prior to the injection of parental (L) spleen cells results in inhibition of the subsequent GVHR to a degree commensurate with the radiation damage sustained by the lymphoid system of the host. Furthermore, propagation of transferred GVHRs did not occur if susceptible secondary hybrid hosts had been previously irradiated. These findings indicate that radiosensitive host cells play a continuing and essential role in the pathogenesis of the invasive-destructive lesion. It is concluded that the development of this lesion depends upon the continuous interaction of the specifically reactive donor-type cells with an immunologically non-specific population of host mononuclears.


Autoimmunity ◽  
2009 ◽  
Vol 42 (4) ◽  
pp. 346-348 ◽  
Author(s):  
B. Frey ◽  
B. Frey ◽  
U. S. Gaipl ◽  
B. Frey ◽  
U. S. Gaipl ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1126
Author(s):  
Kyung-Hee Song ◽  
Seung-Youn Jung ◽  
Jeong-In Park ◽  
Jiyeon Ahn ◽  
Jong-Kuk Park ◽  
...  

Low-dose irradiation (LDI) has recently been shown to have various beneficial effects on human health, such as on cellular metabolic activities, DNA repair, antioxidant activity, homeostasis potency, and immune activation. Although studies on the immunogenic effects of LDI are rapidly accumulating, clinical trials for cancer treatment are considered premature owing to the lack of available preclinical results and protocols. Here, we aim to investigate anti-tumor and anti-metastatic effects of whole-body LDI in several tumor-bearing mouse models. Mice were exposed to single or fractionated whole-body LDI prior to tumor transplantation, and tumor growth and metastatic potential were determined, along with analysis of immune cell populations and expression of epithelial–mesenchymal transition (EMT) markers. Whole-body fractionated-LDI decreased tumor development and lung metastasis not only by infiltration of CD4+, CD8+ T-cells, and dendritic cells (DCs) but also by attenuating EMT. Moreover, a combination of whole-body LDI with localized high-dose radiation therapy reduced the non-irradiated abscopal tumor growth and increased infiltration of effector T cells and DCs. Therefore, whole-body LDI in combination with high-dose radiation therapy could be a potential therapeutic strategy for treating cancer.


Circulation ◽  
1996 ◽  
Vol 93 (3) ◽  
pp. 529-536 ◽  
Author(s):  
John R. Laird ◽  
Andrew J. Carter ◽  
William M. Kufs ◽  
Timothy G. Hoopes ◽  
Andrew Farb ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adem T. Can ◽  
Daniel F. Hermens ◽  
Megan Dutton ◽  
Cyrana C. Gallay ◽  
Emma Jensen ◽  
...  

AbstractRecently, low-dose ketamine has been proposed as a rapid-acting treatment option for suicidality. The majority of studies to date have utilised intravenous (IV) ketamine, however, this route of administration has limitations. On the other hand, oral ketamine can be administered in a range of settings, which is important in treating suicidality, although studies as to safety and feasibility are lacking. n = 32 adults (aged 22–72 years; 53% female) with chronic suicidal thoughts participated in the Oral Ketamine Trial on Suicidality (OKTOS), an open-label trial of sub-anaesthetic doses of oral ketamine over 6 weeks. Participants commenced with 0.5 mg/kg of ketamine, which was titrated to a maximum 3.0 mg/kg. Follow-up assessments occurred at 4 weeks after the final dose. The primary outcome measure was the Beck Scale for Suicide Ideation (BSS) and secondary measures included scales for suicidality and depressive symptoms, and measures of functioning and well-being. Mean BSS scores significantly reduced from a high level of suicidal ideation at the pre-ketamine (week 0) timepoint to below the clinical threshold at the post-ketamine (week 6) timepoint. The proportion of participants that achieved clinical improvement within the first 6 weeks was 69%, whereas 50% achieved a significant improvement by the follow-up (week 10) timepoint. Six weeks of oral ketamine treatment in participants with chronic suicidality led to significant reduction in suicidal ideation. The response observed in this study is consistent with IV ketamine trials, suggesting that oral administration is a feasible and tolerable alternative treatment for chronic suicidality.


Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582097313
Author(s):  
Dario Baldi ◽  
Liberatore Tramontano ◽  
Vincenzo Alfano ◽  
Bruna Punzo ◽  
Carlo Cavaliere ◽  
...  

For decades, the main imaging tool for multiple myeloma (MM) patient’s management has been the conventional skeleton survey. In 2014 international myeloma working group defined the advantages of the whole-body low dose computed tomography (WBLDCT) as a gold standard, among imaging modalities, for bone disease assessment and subsequently implemented this technique in the MM diagnostic workflow. The aim of this study is to investigate, in a group of 30 patients with a new diagnosis of MM, the radiation dose (CT dose index, dose-length product, effective dose), the subjective image quality score and osseous/extra-osseous findings rate with a modified WBLDCT protocol. Spectral shaping and third-generation dual-source multidetector CT scanner was used for the assessment of osteolytic lesions due to MM, and the dose exposure was compared with the literature findings reported until 2020. Mean radiation dose parameters were reported as follows: CT dose index 0.3 ± 0.1 mGy, Dose-Length Product 52.0 ± 22.5 mGy*cm, effective dose 0.44 ± 0.19 mSv. Subjective image quality was good/excellent in all subjects. 11/30 patients showed osteolytic lesions, with a percentage of extra-osseous findings detected in 9/30 patients. Our data confirmed the advantages of WBLDCT in the diagnosis of patients with MM, reporting an effective dose for our protocol as the lowest among previous literature findings.


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