Single blood transfusion induces the production of donor-specific alloantibodies and regulatory T cells mainly in the spleen

Ueta, Hisashi; Kitazawa, Yoshiaki; Sawanobori, Yasushi; Ueno, Takamasa; Ueha, Satoshi; Matsushima, Kouji; Matsuno, Kenjiro

doi:10.1093/intimm/dxx078

Cited by 10 publications

(25 citation statements)

References 26 publications

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“…When activation state of DC subsets was examined 36 h after transfer of CFSE-labeled donor TDLs, CFSE + XCR1 + DCs showed a significant upregulation of CD40 (Figures 7A,B), although CFSE − XCR1 + and CFSE − XCR1 − DCs showed no change (Figure S6). CD103 + DCs readily formed clusters with proliferating cells in the PALS 2 days after DST (Figures 7C,D), which was composed mostly of CD4 + T cells as reported previously (24). Although we observed selective phagocytosis of donor cells by XCR1 + DCs (Figure 3), not only XCR1 + DCs (~50%), but also XCR1 − DCs (~16%) formed clusters with recipient EdU + proliferating cells in the PALS (Figures 7E,F).…”

Section: Resultssupporting

confidence: 85%

“…For the most part, these conditions were observed in the present study (Figure 10). We have already demonstrated the final step (24). For the preceding steps, XCR1 + DCs may present donor MHCI antigens after phagocytosis and processing of donor T cell fragments.…”

Section: Discussionmentioning

confidence: 90%

“…prior to transplantation, is one of the tolerance-inducing protocols used in not only experimental (22), but also clinical (23) transplantation. Recently, we demonstrated that a single DST efficiently induces a helper T cell-dependent anti-donor class I MHC (MHCI) antibody-forming cell and donor-specific regulatory T cell responses, mainly in the spleen (24). Notably, we also found that these antibodies were still produced after DST even in splenectomized recipients.…”

Section: Introductionmentioning

confidence: 99%

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Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes

et al. 2019

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Vaccination strategy that induce efficient antibody responses polytopically in most lymph nodes (LNs) against infections has not been established yet. Because donor-specific blood transfusion induces anti-donor class I MHC antibody production in splenectomized rats, we examined the mechanism and significance of this response. Among the donor blood components, T cells were the most efficient immunogens, inducing recipient T cell and B cell proliferative responses not only in the spleen, but also in the peripheral and gut LNs. Donor T cells soon migrated to the splenic T cell area and the LNs, with a temporary significant increase in recipient NK cells. XCR1 + resident dendritic cells (DCs), but not XCR1 − DCs, selectively phagocytosed donor class I MHC + fragments after 1 day. After 1.5 days, both DC subsets formed clusters with recipient CD4 + T cells, which proliferated within these clusters. Inhibition of donor T cell migration or depletion of NK cells by pretreatment with pertussis toxin or anti-asialoGM 1 antibody, respectively, significantly suppressed DC phagocytosis and subsequent immune responses. Three allogeneic strains with different NK activities had the same response but with different intensity. Donor T cell proliferation was not required, indicating that the graft vs. host reaction is dispensable. Intravenous transfer of antigen-labeled and mitotic inhibitor-treated allogeneic, but not syngeneic, T cells induced a polytopical antibody response to labeled antigens in the LNs of splenectomized rats. These results demonstrate a novel mechanism of alloresponses polytopically in the secondary lymphoid organs (SLOs) induced by allogeneic T cells. Donor T cells behave as self-migratory antigen ferries to be delivered to resident XCR1 + DCs with negligible commitment of migratory DCs. Allogeneic T cells may be clinically applicable as vaccine vectors for polytopical prophylactic antibody production even in asplenic or hyposplenic individuals.

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Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes

et al. 2019

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“…Zhang et al adversely affected the patients' survival. 32,33 Anyway, unnecessary transfusions should be avoided to reduce the occurrence of bacteremia in hospital. 34,35 Additionally, hospitalization in CJFH is noted to have a higher death risk than other centers in this study.…”

Section: Dovepressmentioning

confidence: 99%

<p>Risk Factors for Mortality of Inpatients with <em>Pseudomonas aeruginosa</em> Bacteremia in China: Impact of Resistance Profile in the Mortality</p>

Zhang¹,

Li²,

Zeng³

et al. 2020

IDR

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Purpose Pseudomonas aeruginosa bacteremia presents a severe challenge to hospitalized patients. However, to date, the risk factors for mortality among inpatients with P. aeruginosa bacteremia in China remain unclear. Patients and Methods This retrospective multicenter study was performed to analyze 215 patients with culture-confirmed P. aeruginosa bacteremia in five healthcare centers in China during the years 2012–2019. Results Of 215 patients with P. aeruginosa bacteremia, 61 (28.4%) died during the study period. Logistic multivariable analysis revealed that cardiovascular disease (OR=3.978, P =0.001), blood transfusion (OR=5.855, P <0.001) and carbapenem-resistant P. aeruginosa (CRPA) phenotype (OR=4.485, P =0.038) constituted the independent risk factors of mortality. Furthermore, both CRPA and multidrug-resistant P. aeruginosa (MDRPA) phenotypes were found to be significantly associated with 5-day mortality (Log-rank, P <0.05). Conclusion This study revealed a high mortality rate amongst hospitalized patients with P. aeruginosa bacteremia, and those with cardiovascular diseases, CRPA and MDRPA phenotypes, should be highlighted and given appropriate management in China.

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“…Other unfavourable phenomena, particularly transfusion-related immunomodulation (TRIM), evolve over a prolonged period [31]. The mechanisms involved in TRIM are not completely understood, but modulation of cellular immunity is suggested to play a key role [32]. The observation that transfusion decreases the probability of rejection of cardiac and renal allografts [33–35] also supports the hypothesis that stored blood cells exert a lasting modulatory effect on immunity.…”

Section: Discussionmentioning

confidence: 99%

Anaemia requiring red blood cell transfusion is associated with unfavourable 90-day survival in surgical patients with sepsis

et al. 2018

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ObjectiveThe mortality associated with sepsis remains unacceptably high, despite modern high-quality intensive care. Based on the results from previous studies, anaemia and its management in patients with sepsis appear to impact outcomes; however, the transfusion policy is still being debated, and the ideal approach may be extremely specific to the individual. This study aimed to investigate the long-term impact of anaemia requiring red blood cell (RBC) transfusion on mortality and disease severity in patients with sepsis. We studied a general surgical intensive care unit (ICU) population, excluding cardiac surgery patients. 435 patients were enrolled in this observational study between 2012 and 2016.ResultsPatients who received RBC transfusion between 28 days before and 28 days after the development of sepsis (n = 302) exhibited a significantly higher 90-day mortality rate (34.1% vs 19.6%; P = 0.004, Kaplan–Meier analysis). This association remained significant after adjusting for confounders in the multivariate Cox regression analysis (hazard ratio 1.68; 95% confidence interval 1.03–2.73; P = 0.035). Patients who received transfusions also showed significantly higher morbidity scores, such as SOFA scores, and ICU lengths of stay compared to patients without transfusions (n = 133). Our results indicate that anaemia and RBC transfusion are associated with unfavourable outcomes in patients with sepsis.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3988-z) contains supplementary material, which is available to authorized users.

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Single blood transfusion induces the production of donor-specific alloantibodies and regulatory T cells mainly in the spleen

Abstract: A single donor-specific transfusion induces alloantibodies and Treg cells

Cited by 10 publications

References 26 publications

Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes

Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes

<p>Risk Factors for Mortality of Inpatients with <em>Pseudomonas aeruginosa</em> Bacteremia in China: Impact of Resistance Profile in the Mortality</p>

Anaemia requiring red blood cell transfusion is associated with unfavourable 90-day survival in surgical patients with sepsis

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