Investigation into the modulation of the red blood cell cytokine profile with non-small cell lung carcinoma and the resulting effect on T-cell activity — ASN Events

Investigation into the modulation of the red blood cell cytokine profile with non-small cell lung carcinoma and the resulting effect on T-cell activity (#270)

Elisabeth Karsten 1 2 3 , Benjamin R. Herbert 1 2 3
  1. Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia
  2. Sangui Bio Pty Ltd, Sydney, NSW, Australia
  3. The Kolling Institute, St Leonards, NSW, Australia

Evidence is mounting that the most abundant cell type in the body, red blood cells (RBCs), are more complex than previously understood. Studies have reported that RBCs from healthy individuals regulate immune cell activity, but stored RBCs or RBCs from inflammatory cohorts are dysfunctional. Those studies did not, however, determine the mode of action that enables RBCs to affect immune cell function. Our group determined that RBCs are the primary reservoir for over 30 cytokines, chemokines, and growth factors in blood. This study aimed to explore the implications of RBC-associated cytokines on immune cell function. RBCs were isolated from healthy volunteers, and cytokine quantification of RBC lysates and secreted cytokines was achieved using Luminex® technology. Exposure to an immortalised cancer cell line in culture was used to alter the cytokine profile of intact RBCs and the effect of these ‘primed’ RBCs on T cells was evaluated using flow cytometry.

Following cell line exposure, primed RBCs were loaded with significant concentrations of cancer-associated cytokines. Then, in the presence of these primed RBCs, T cells (Jurkat cells and peripheral blood mononucleated cells) proliferated significantly more than naïve RBC stimulated controls, were no longer protected from stimulant-driven activation, and secreted a variety of cancer-related cytokines. This study supports the hypothesis that RBCs act as a dynamic buffer for cytokines in blood through binding and release, and that RBCs affect the activity of immune cells. Cell-cell interactions alter RBC cytokine profiles and modulate their effect on immune cells. These findings may have implications in the study of the storage lesion and the inflammatory processes that can occur following RBC transfusion.

  1. Antunes, R. F., Brandão, C., Maia, M. & Arosa, F. A. Red blood cells release factors with growth and survival bioactivities for normal and leukemic T cells. Immunol. Cell Biol. 89, 111–121 (2011).
  2. Buttari, B. et al. Erythrocytes from patients with carotid atherosclerosis fail to control dendritic cell maturation. Int. J. Cardiol. 155, 484–486 (2012).
  3. Long, K. et al. T-cell suppression by red blood cells is dependent on intact cells and is a consequence of blood bank processing. Transfusion 54, 1340–1347 (2014).
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