Platelet transfusion-related immunomodulation in mice: shift in monocyte/macrophage populations during refractoriness in mice
ROJAS-JIMÉNEZ G. 1,2,3, COUVIDOU A. 1,2,3, SAYAH M. 1,2,3, ANGÉNIEUX C. 1,2,3, MAÎTRE B. 1,2,3
1 Établissement Français du Sang, Strasbourg, France; 2 INSERM UMR_S 1255, Strasbourg, France; 3 Université de Strasbourg, Strasbourg, France
Platelet transfusion is a lifesaving procedure for patients who are bleeding or at high risk of bleeding. In some patients, transfused platelets are rapidly removed from the circulation because of anti-HLA class I alloantibodies, leading to therapeutic failure, in a condition known as refractoriness. One hypothesis to explain this variability in transfusion efficiency among immunized patients could be a platelet transfusion-related immunomodulation (pTRIM), which may occur only in certain subjects.
To characterize pTRIM, we studied the shift in blood monocyte and immune liver cells populations during platelet transfusion refractoriness.
Platelet transfusion refractoriness was mimicked by transfusing allogeneic H2b-platelets into a recipient H2d-mouse previously immunized against H2b-platelets. Blood and liver were sampled 30 min after platelet transfusion. Monocytes and liver immune cells were analyzed by flow cytometry based on expression of CD45, CD115, CD11b, LY6C, CD62L; or F4/80 and CD11b, respectively.
Transfused platelets circulated for 3 days in naïve mice whereas they were eliminated from circulation within the first 30 minutes in alloimmunized mice, revealing a refractory state. Flow cytometry on peripheral blood showed a decrease of 59% in the proportion of circulating CD45+ CD62L+ Ly6Chigh cells 30 min after platelet transfusion in refractory mice. Interestingly, pTRIM was more important in immunized mice than in naïve mice. In parallel, we observed an increase in at least double the proportion of F4/80-CD11b+ liver cells in refractory mice as compared to naïve mice, suggesting a possible recruitment of circulating blood cells during refractoriness.
Our results showed a compelling change both in circulating monocytes and in hepatic immune cells in refractory mice following allogeneic platelet transfusion. This shift could hint towards a possible recruitment of circulating blood cells during refractoriness, thereby reflecting immunomodulation under these circumstances.