Packed Red Blood Cells Suppress T-Cell Proliferation Through a Process Involving Cell–Cell Contact

Bernard, Andrew C.; Meier, Cindy; Ward, Marty; Browning, Tyler; Montgomery, Ashley; Kasten, Michael W.; Snow, Charles C.; Manning, Erin; Woodward, Jerold G.

doi:10.1097/ta.0b013e3181e401f0

Cited by 29 publications

(34 citation statements)

References 21 publications

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“…These results are similar to a previous study which focused on responses to PC supernatants [168]. [79,80,88,289]. While changes in the overall leukocyte inflammatory response were evident, it is important to consider these results predominantly represent the response of the more abundant leukocyte subsets, such as neutrophils and lymphocytes.…”

Section: Discussionsupporting

confidence: 77%

“…A more recent study indicates B and T lymphocyte proliferation was suppressed following exposure to leukodepleted PRBC stored for two to three weeks, but not freshly collected leukodepleted RBC [88]. Suppression of T lymphocyte proliferation has also been reported in studies utilising PRBC in a whole blood model [84], and in a cell culture model utilising PRBC supernatants and Jurkat T lymphocytes [80].…”

Section: In-vitro and In-vivo Models Of Prbc Transfusion (Related To mentioning

confidence: 90%

“…I found minimal modulation of cytokine responses following exposure to PRBC alone, however, both mDC and BDCA3 + DC responses to polyI:C and LPS were suppressed in the presence of PRBC. Together poor co-stimulation and lack of cytokine and chemokine production may be associated with inadequate T and B lymphocyte responses [79,80,88] and my data suggest PRBC transfusion has the potential to impair downstream lymphocyte responses.…”

Section: Prbc Storage Was Associated With Increased Erythrophagocytosismentioning

confidence: 99%

“…Increased monocyte erythrophagocytosis of stored PRBC has also been reported [283]. Transfusion-related modulation of immune responses are not limited to innate cells, with exposure to PRBC reported to increase CD25 + regulatory T lymphocyte production, reduce the number of responder T lymphocytes [79], and suppress B and T lymphocyte proliferation [80,88]. To date, studies assessing the role of DC in transfusion outcomes are limited.…”

Section: Introductionmentioning

confidence: 99%

“…The potential for PRBC to modulate recipients' immune response and impact patient outcomes has been studied using in-vitro [79][80][81][82][83][84][85][86][87][88][89] and in-vivo [90] models. An in-vitro study using a whole blood model reported increased interleukin (IL)-10 production and reduced tumour necrosis factor (TNF)-α production by the overall leukocytes in the culture supernatant following 24 h exposure to either autologous or allogeneic PRBC [81].…”

Section: In-vitro and In-vivo Models Of Prbc Transfusion (Related To mentioning

confidence: 99%

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Characterisation of dendritic cell immune profile in models of transfusion

Ki¹

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Blood transfusion modulates recipients' immune responses sometimes resulting in poor clinical outcomes. Further, transfusion with blood products at date-of-expiry has been associated with exacerbation of this concerning problem. In-vitro studies have demonstrated exposure to packed red blood cell (PRBC) and platelet products modulate the responses of leukocytes, however, there are limited studies on the impact of transfusion on dendritic cells (DC). Despite DC being central to the immune response, their role in transfusion-related immune modulation remains largely undefined. I hypothesised that exposure to blood components changes DC phenotype and function, which could be one mechanism underpinning transfusion-related immune modulation. The potential for blood components (PRBC, buffy-coat-derived platelet concentrates (PC) and cryopreserved platelets (cryo-PLT)) to modulate responses of myeloid dendritic cells ii whether blood components exposing F-actin for Clec9A ligation were present within the blood product. rhClec9A did not bind fresh or stored PRBC, and this outcome was supported by the lack of detection of F-actin. Although, no binding of rhClec9A to PC or cryo-PLT was demonstrated, F-actin was detected on both types of platelet products. As binding of rhClec9A to PRBC, PC or cryo-PLT was not detected, EDTA blood collection tubes were used for the remainder of the study under the premise that lack of expression of this receptor would not impact on outcomes in my transfusion models.I assessed the impact of fresh and/or stored blood products on mDC and BDCA3 + DC surface antigen and inflammatory profile using a human in-vitro whole blood model of transfusion. In parallel, to model the processes associated with viral or bacterial infection, polyinosinic:polycytidylic acid (polyI:C) or lipopolysaccharide (LPS) was added respectively. Exposure to PRBC and PC predominately suppressed surface antigen expression (CD40, CD80, CD83 and CD86) and inflammatory mediator production (interleukin (IL)-6, IL-8, IL-12, tumour necrosis factor-α and interferon-gamma inducible protein-10 or IL-10) on both DC subsets. These changes were often more evident in the presence of polyI:C and LPS, and when DC were exposed to stored PRBC. Similar modulation was evident for BDCA3 + DC when exposed to cryo-PLT alone and cryo-PLT in the presence of polyI:C and LPS. The impact of blood transfusion on the overall inflammatory response by leukocytes was also examined. The immunomodulatory effect of transfusion in-vitro was more pronounced in the presence of polyI:C and LPS. For PRBC, an additional erythrophagocytosis assay was conducted where the uptake of stored PRBC by mDC and BDCA3 + DC was significantly increased in comparison to fresher PRBC.This study provided the first evidence that exposure of PRBC, PC and cryo-PLT modulates mDC and/or BDCA3 + DC maturation and activation. The changes were more pronounced when modelling processes associated with concurrent viral or bacterial infection.Experimental evidence suggested that mod...

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Section: Discussionsupporting

confidence: 77%

Section: In-vitro and In-vivo Models Of Prbc Transfusion (Related To mentioning

confidence: 90%

Section: Prbc Storage Was Associated With Increased Erythrophagocytosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: In-vitro and In-vivo Models Of Prbc Transfusion (Related To mentioning

confidence: 99%

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Characterisation of dendritic cell immune profile in models of transfusion

Ki¹

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Durable immune response to inactivated H1N1 vaccine is less likely in children with sickle cell anemia receiving chronic transfusions

Purohit

Álvarez

O’Brien

et al. 2012

Pediatric Blood & Cancer

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Most subjects were able to mount an influenza-specific antibody response against the inactivated H1N1 vaccine. Similar to the general population, children less than 3 years were less likely to respond. In addition, patients on chronic transfusions were less likely to respond when compared to non-transfused children. Clinicians should be aware of the possibility of decreased vaccine response in patients with SCD on chronic transfusions. We postulate that transfusion-related immunomodulation (TRIM) may be related to decreased response.

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Arginine in Critical Care: Preclinical Aspects

Gautier

2015

Diet and Nutrition in Critical Care

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Packed Red Blood Cells Suppress T-Cell Proliferation Through a Process Involving Cell–Cell Contact

Abstract: PRBC suppresses mitogen-stimulated human and antigen-stimulated mouse T-cell proliferation by mechanisms independent of arginine depletion. This is a novel mechanism for transfusion-associated immune suppression.

Cited by 29 publications

References 21 publications

Characterisation of dendritic cell immune profile in models of transfusion

Characterisation of dendritic cell immune profile in models of transfusion

Durable immune response to inactivated H1N1 vaccine is less likely in children with sickle cell anemia receiving chronic transfusions

Arginine in Critical Care: Preclinical Aspects

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