Packed red blood cells suppress T-cell proliferation through a process involving cell-cell contact.

Published

Journal Article

BACKGROUND: Packed red blood cell (PRBC) transfusion suppresses immunity and increases morbidity and mortality. Leukocyte reduction has failed to abrogate these effects, thus implicating red blood cells themselves or their components. PRBC impair proliferation of immortal (Jurkat) T cells by depleting arginine from the extracellular environment. The effect of PRBC on isolated ex vivo T-cell proliferation has not been reported. We hypothesize that PRBCs depress mitogen-stimulated proliferation in isolated human and mouse T cells. METHODS: Human peripheral T cells were isolated by Ficoll-Hypaque gradient, purified by magnetic separation, and stimulated with anti-CD3 or anti-CD28. DO11.10 transgenic mouse splenic T cells were stimulated with ovalbumin. Cells were cultured at 1 x 10(6)/mL in 96-well plates or in 24-transwell plates in the presence of PRBC (0.015-5% by volume, stored for 4-6 weeks). In culture media, arginine and citrulline were varied. Proliferation was measured at 72 hours by thymidine incorporation. T-cell viability, apoptosis, and receptor zeta chain were measured by flow cytometry. RESULTS: PRBC significantly depressed human peripheral and mouse splenic T-cell proliferation in a dose-dependent manner. PRBC arginase blockade by N-omega-hydroxy-nor-l-arginine only partly restored proliferation. Cell contact was required in both cell types for maximal effect. Depressed zeta chain in human peripheral T cells was partly restored by arginase blockade. Salvage by high-dose arginine and citrulline was unsuccessful. Decreased proliferation was not related to cell death. CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Bernard, A; Meier, C; Ward, M; Browning, T; Montgomery, A; Kasten, M; Snow, C; Manning, E; Woodward, J

Published Date

  • August 2010

Published In

Volume / Issue

  • 69 / 2

Start / End Page

  • 320 - 329

PubMed ID

  • 20699740

Pubmed Central ID

  • 20699740

Electronic International Standard Serial Number (EISSN)

  • 1529-8809

Digital Object Identifier (DOI)

  • 10.1097/TA.0b013e3181e401f0

Language

  • eng

Conference Location

  • United States