Pathogen-reduced PRP blocks T-cell activation, induces Treg cells, and promotes TGF-β expression by cDCs and monocytes in mice

Abstract

Alloimmunization against platelet-rich plasma (PRP) transfusions can lead to complications such as platelet refractoriness or rejection of subsequent transfusions and transplants. In mice, pathogen reduction treatment of PRP with UVB light and riboflavin (UV+R) prevents alloimmunization and appears to induce partial antigen-specific tolerance to subsequent transfusions. Herein, the in vivo responses of antigen-presenting cells and T cells to transfusion with UV+R-treated allogeneic PRP were evaluated to understand the cellular immune responses leading to antigen-specific tolerance. Mice that received UV+R-treated PRP had significantly increased transforming growth factor β (TGF-β) expression by CD11b+ CD4+ CD11cHi conventional dendritic cells (cDCs) and CD11bHi monocytes (P < .05). While robust T-cell responses to transfusions with untreated allogeneic PRP were observed (P < .05), these were blocked by UV+R treatment. Mice given UV+R-treated PRP followed by untreated PRP showed an early significant (P < .01) enrichment in regulatory T (Treg) cells and associated TGF-β production as well as diminished effector T-cell responses. Adoptive transfer of T-cell–enriched splenocytes from mice given UV+R-treated PRP into naive recipients led to a small but significant reduction of CD8+ T-cell responses to subsequent allogeneic transfusion. These data demonstrate that pathogen reduction with UV+R induces a tolerogenic profile by way of CD11b+ CD4+ cDCs, monocytes, and induction of Treg cells, blocking T-cell activation and reducing secondary T-cell responses to untreated platelets in vivo.

Amniotic fluid allograft enhances the host response to ventral hernia repair using acellular dermal matrix

“…That is, Amnion is a human‐derived product that was implanted in Lewis rats in this study. As previously demonstrated (Tran et al., 2020), allogeneic fluid transplants can lead to CD8 + T cell infiltration via dendritic cell activation secondary to macrophage activity. While Tran et al.…”

“…An important limitation of this study is that the AFA implanted in the Lewis rats represents an allogeneic transplantation known to result in increased macrophage and cytotoxic T cell activation (Tran et al., 2020). Decoupling the effects of T cell mediated wound response from the indirect effects mediated by T cell and macrophage cooperativity was outside the scope of this pilot study, and we instead focused specifically on the effects of M2 macrophage impacts on the wound healing environment.…”

Platelet rich plasma concentration improves biologic mesh incorporation and decreases multinucleated giant cells in a dose dependent fashion

“…Thus, a combinatorial effect not only on attraction of CD8+ T cells to the wound site, but also on the remodeling of the surrounding matrix (Juric et al, 2018), could be reasonably expected in response to PRP treatment. Prior studies have shown that pathogen-reduction of PRP by UV exposure reduces T cell activation in a mouse model (Tran et al, 2020). Thus, in addition to the possible role of TGFβ discussed above, the PRP used in this study may increase dendritic cell activation secondary to macrophage activity at the mesh implantation site, thus leading to increased CD8 + T cell activation and infiltration at high doses of PRP.…”

Polyinosinic: polycytidylic acid induced inflammation enhances while lipopolysaccharide diminishes alloimmunity to platelet transfusion in mice

“…Blood from B6 donor mice was collected by orbital enucleation under inhalation isoflurane anesthesia into 14% citrate phosphate dextrose adenine-1, and non-leukoreduced platelets were isolated from blood after gentle centrifugation and Ficoll separation as previously described ( 5 , 17 , 37 – 41 ). Complete blood counts (CBCs) were run on the HT-5 (Heska) according to manufacturer’s instructions.…”