High‐level long‐term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury

Lee, Tzong Hae; Paglieroni, Teresa; Utter, Garth H.; Chafets, Daniel M.; Gosselin, Robert; Reed, William; Owings, John T.; Holland, Paul V.; Busch, Michael P.

doi:10.1111/j.1537-2995.2005.00201.x

Cited by 92 publications

(125 citation statements)

References 31 publications

(34 reference statements)

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…Indeed, several studies suggest that allogeneic blood transfusions in cancer and trauma patients correlate with the induction of microchimerism and with downregulation of the immune response, due to repeated exposure to foreign antigens. 46,47 However, in our study the proportion of Tr1 cell clones detected before the transplant was comparable to that in normal donors, suggesting that multiple transfusions prior to the transplant should not have contributed to the induction of IL-10 production. Since not all thalassemic patients with mixed chimerism early after the transplant develop PMC, 5,6 it is possible that multiple factors are involved in the establishment of long-term tolerance.…”

Section: Discussionmentioning

confidence: 45%

Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia

Serafini¹,

Andreani²,

Testi³

et al. 2009

Haematologica

View full text Add to dashboard Cite

BackgroundThalassemia major can be cured with allogeneic hematopoietic stem cell transplantation. Persistent mixed chimerism develops in around 10% of transplanted thalassemic patients, but the biological mechanisms underlying this phenomenon are poorly understood. Design and MethodsThe presence of interleukin-10-producing T cells in the peripheral blood of eight patients with persistent mixed chimerism and five with full donor chimerism was investigated. A detailed characterization was then performed, by T-cell cloning, of the effector and regulatory T-cell repertoire of one patient with persistent mixed chimerism, who developed stable split erythroid/lymphoid chimerism after a hematopoietic stem cell transplant from an HLA-matched unrelated donor. ResultsHigher levels of interleukin-10 were produced by peripheral blood mononuclear cells from patients with persistent mixed chimerism than by the same cells from patients with complete donor chimerism or normal donors. T-cell clones of both host and donor origin could be isolated from the peripheral blood of one, selected patient with persistent mixed chimerism. Together with effector T-cell clones reactive against host or donor alloantigens, regulatory T-cell clones with a cytokine secretion profile typical of type 1 regulatory cells were identified at high frequencies. Type 1 regulatory cell clones, of both donor and host origin, were able to inhibit the function of effector T cells of either donor or host origin in vitro. ConclusionsOverall these results suggest that interleukin-10 and type 1 regulatory cells are associated with persistent mixed chimerism and may play an important role in sustaining long-term tolerance in vivo. These data provide new insights into the mechanisms of peripheral tolerance in chimeric patients and support the use of cellular therapy with regulatory T cells following hematopoietic stem cell transplantation.Key words: thalassemia, hematopoietic stem cell transplantation, persistent mixed chimerism, tolerance, type 1 regulatory T (Tr1) cells.Citation: Serafini G, Andreani M, Testi M, Battarra MR, Bontadini A, Biral E, Fleischhauer K, Marktel S, Lucarelli G, Roncarolo MG, and

show abstract

Section: Discussionmentioning

confidence: 45%

Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia

Serafini¹,

Andreani²,

Testi³

et al. 2009

Haematologica

View full text Add to dashboard Cite

show abstract

“…Total proviral HIV DNA was extracted from PBMCs by using modifications of previously described methods (34). This assay has an overall sensitivity of 1 copy/3 g of input DNA, equivalent to approximately 450,000 PBMCs (33,35). All proviral DNA levels were normalized to the input number of PBMCs.…”

Section: Methodsmentioning

confidence: 99%

Evidence for Persistent Low-Level Viremia in Individuals Who Control Human Immunodeficiency Virus in the Absence of Antiretroviral Therapy

Hatano

Delwart

Norris

et al. 2009

J Virol

Self Cite

185

182

View full text Add to dashboard Cite

A subset of antiretroviral-untreated, human immunodeficiency virus (HIV)-infected individuals are able to maintain undetectable plasma HIV RNA levels in the absence of antiretroviral therapy. These "elite" controllers are of high interest as they may provide novel insights regarding host mechanisms of virus control. The degree to which these individuals have residual plasma viremia has not been well defined. We performed a longitudinal study of 46 elite controllers, defined as HIV-seropositive, antiretroviral-untreated individuals with plasma HIV RNA levels of <50 to 75 copies/ml. The median duration of HIV diagnosis was 13 years, the median baseline CD4؉ T-cell count was 753 cells/mm 3 , and the median duration of follow-up was 16 months. Plasma and cellular HIV RNA levels were measured using the transcription-mediated amplification (TMA) assay (estimated limit of detection of <3.5 copies RNA/ml). A total of 1,117 TMA assays were performed (median of five time points/subject and four replicates/time point). All but one subject had detectable plasma HIV RNA on at least one time point, and 15 (33%) subjects had detectable RNA at all time points. The majority of controllers also had detectable cell-associated RNA and proviral DNA. A mixed-effect linear model showed no strong evidence of change in plasma RNA levels over time. In conclusion, the vast majority (98%) of elite controllers had measurable plasma HIV RNA, often at levels higher than that observed in antiretroviraltreated patients. This confirms the failure to eradicate the virus, even in these unique individuals who are able to reduce plasma viremia to very low levels without antiretroviral therapy.

show abstract

“…Transfusion-associated microchimerism is present in approximately 50% of transfused severely injured patients at hospital discharge and is not affected by leukoreduction [55]. It is postulated that, if the conditions are right for transfusion-associated microchimerism to develop, engraftment occurs with a very small number of pluripotent hematopoietic cells, regardless of the total number of donor WBCs present.…”

Section: Immunosuppressionmentioning

confidence: 99%

Transfusion-transmissible infections and transfusion-related immunomodulation

Buddeberg

Schimmer

Spahn

2008

Best Practice & Research Clinical Anaesthesiology

View full text Add to dashboard Cite

Transfusion-transmissible infections and transfusion-related immunomodulation AbstractThe risk of acquiring a transfusion-transmitted infection has declined in recent years. However, after human immunodeficiency virus and hepatitis B and C virus transmission were successfully reduced, new pathogens are threatening the safety of the blood supply, especially in the face of rising numbers of immunocompromised transfusion recipients. Despite new standards in the manufacture and storage of blood products, bacterial contamination still remains a considerable cause of transfusion-related morbidity and mortality. Better allograft survival in kidney transplant patients and higher cancer recurrence rate in surgical oncology patients after allogeneic blood transfusions highlighted a previously underestimated side-effect: transfusion-related immunomodulation (TRIM). The precise pathomechanism still remains uncertain; however, its mostly deleterious effects--such as a higher incidence of postoperative or nosocomial infections--is increasingly accepted. Although transfusion-related immunomodulation is thought to be mediated mainly by donor white blood cells, the benefit of leukoreduction on overall mortality and on infectious complications is highly debatable. Transfusion-transmissible infections and Transfusion-related immunomodulation Transfusion-transmissible infections and Transfusion-related immunomodulation AbstractThe risk of acquiring a transfusion-transmitted infection has declined in recent years.

show abstract

High‐level long‐term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury

Cited by 92 publications

References 31 publications

Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia

Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia

Evidence for Persistent Low-Level Viremia in Individuals Who Control Human Immunodeficiency Virus in the Absence of Antiretroviral Therapy

Transfusion-transmissible infections and transfusion-related immunomodulation

Contact Info

Product

Resources

About