Cell-based immunotherapies can provide safe and effective treatments for various disorders including autoimmunity, cancer, and excessive proinflammatory events in sepsis or viral infections. However, to achieve this goal there is a need for deeper understanding of mechanisms of the intercellular interactions. Regulatory T cells (Tregs) are a lymphocyte subset that maintain peripheral tolerance, whilst mesenchymal stem cells (MSCs) are multipotent nonhematopoietic progenitor cells. Despite coming from different origins, Tregs and MSCs share immunoregulatory properties that have been tested in clinical trials. Here we demonstrate how direct and indirect contact with allogenic MSCs improves Tregs’ potential for accumulation of immunosuppressive adenosine and suppression of conventional T cell proliferation, making them more potent therapeutic tools. Our results also demonstrate that direct communication between Tregs and MSCs is based on transfer of active mitochondria and fragments of plasma membrane from MSCs to Tregs, an event that is HLA-dependent and associates with HLA-C and HLA-DRB1 eplet mismatch load between Treg and MSC donors.

Preeclampsia (PE) is a disorder that affects 3–5% of normal pregnancies. It was believed for a long time that the kidney, similarly to all vessels in the whole system, only sustained endothelial damage. The current knowledge gives rise to a presumption that the main role in the development of proteinuria is played by damage to the podocytes and their slit diaphragm. The podocyte damage mechanism in preeclampsia is connected to free VEGF and nitric oxide (NO) deficiency, and an increased concentration of endothelin-1 and oxidative stress. From national cohort studies, we know that women who had preeclampsia in at least one pregnancy carried five times the risk of developing end-stage renal disease (ESRD) when compared to women with physiological pregnancies. The focal segmental glomerulosclerosis (FSGS) is the dominant histopathological lesion in women with a history of PE. The kidney’s podocytes are not subject to replacement or proliferation. Podocyte depletion exceeding 20% resulted in FSGS, which is a reason for the later development of ESRD. In this review, we present the mechanism of kidney (especially podocytes) injury in preeclampsia. We try to explain how this damage affects further changes in the morphology and function of the kidneys after pregnancy.

Introduction: CD4+ T regulatory cells (Tregs) have been described as the most potent immunosuppressive cells in the human body. They have been found to control autoimmunity, and clinical attempts have been made to apply them to treat autoimmune diseases. Some specific pathways utilized by Tregs in the regulation of immune response or Tregs directly as cellular products are tested in the clinic. Areas covered: Here, we present recent advances in the research on the biology and clinical applications of Tregs in the treatment of autoimmune diseases. Expert opinion: Regulatory T cells seem to be a promising tool for the treatment of autoimmune diseases. The development of both cell-based therapies and modern pharmacotherapies which affect Tregs may strongly improve the treatment of autoimmune disorders. Growing knowledge about Treg biology together with the latest biotechnology tools may give an opportunity for personalized therapies in these conditions.

Rheumatoid arthritis is a severe chronic autoimmune disorder that results from pathological activation of immune cells and altered cytokine/chemokine network. The aim of our study was to evaluate concentrations of chosen cytokines and chemokines in blood sera and synovial fluid samples isolated from low disease activity rheumatoid arthritis (RA) patients and osteoarthritis (OA) sufferers. Blood sera and synovial fluid samples have been obtained from 24 OA and 14 RA patients. Cytokines/chemokines levels have been determined using a Milliplex^®Map 38-plex human cytokine/chemokine magnetic bead-based panel (Merck Millipore, Germany) and Luminex^®MAGPIX^®platform (Luminex USA). Low disease activity RA patients showed altered concentration of numerous cytokine/chemokine when compared to OA controls—they were characterized by, inter alia, increased: eotaxin/CCL11 (p = 0.037), GRO/CXCL1 (p = 0.037), IL-2 (p = 0.013), IL-4 (p = 0.017), IL-7 (p = 0.003), IL-8 (p = 0.0007) and GM-CSF (p = 0.037) serum levels, whilst MDC/CCL22 concentration was decreased in this group (p = 0.034). Eotaxin/CCL11 (p = 0.001), GRO/CXCL1 (p = 0.041), IL-10 (p = 0.003), GM-CSF (p = 0.01), IL-1RA (p = 0.0005) and VEGF (p = 0.01) concentrations in synovial fluid of RA females were also increased. Even with low disease activity score, RA patients exhibited increased concentrations of cytokines with pro- and anti-inflammatory activities, as well as numerous chemokines, growth factors and regulators of angiogenesis. Surprisingly, RA subjects also shown decreased concentration of CCL22 chemokine. The attempt to restore cytokine balance and tolerogenic environment is ineffective in RA sufferers even with good disease management. Distinguished factors could serve as possible indicators of disease progression even in low disease activity patients.

Cornea is one of the most commonly transplanted tissues worldwide. However, it is usually omitted in the field of transplantology. Transplantation of the cornea is performed to treat many ocular diseases. It restores eyesight significantly improving the quality of life. Advancements in banking of explanted corneas and progressive surgical techniques increased availability and outcomes of transplantation. Despite the vast growth in the field of transplantation laboratory testing, standards for corneal transplantation still do not include HLA typing or alloantibody detection. This standard practice is based on immune privilege dogma that accounts for high success rates of corneal transplantation. However, the increasing need for retransplantation in high-risk patients with markedly higher risk of rejection causes ophthalmology transplantation centers to reevaluate their standard algorithms. In this review we discuss immune privilege mechanisms influencing the allograft acceptance and factors disrupting the natural immunosuppressive environment of the eye. Current developments in testing and immunosuppressive treatments (including cell therapies), when applied in corneal transplantation, may give very good results, decrease the possibility of rejection, and reduce the need for retransplantation, which is fairly frequent nowadays.

Corneal transplantations (CTXs) are a vision-saving procedure. Routinely, while CTXs' survival rates remain high, the risk of graft failure increases significantly for repeated CTXs. The reason is an alloimmunization following previous CTXs and development of memory T (Tm) and B (Bm) cells. We characterized populations of cells present in explanted human corneas from patients receiving the first CTX and marked as a primary CTX (PCTX) or the second or more CTXs and marked as a repeated CTX (RCTX). Cells extracted from resected corneas and from peripheral blood mononuclear cells (PBMCs) were analyzed by the flow cytometry method using multiple surface and intracellular markers. Overall, the number of cells was similar in PCTX and RCTX patients. Extracted infiltrates from PCTXs and RCTXs contained similar numbers of T cell subsets, namely CD4+, CD8+, CD4+ Tm, CD8+ Tm, CD4+Foxp3+ T regulatory (Tregs), CD8+ Treg cells, while very few B cells (all p = NS). However, when compared to peripheral blood, PCTX and RCTX corneas contained significantly higher percentages of effector memory CD4+ and CD8+ T cells (both p < 0,05). In comparison to PCTX, RCTX group had the highest levels of Foxp3 in T CD4+ Tregs (p = 0,04) but decreased percentage of Helios-positive CD4+ Tregs. PCTXs and especially RCTXs are rejected mainly by local T cells. The accumulation of effector CD4+ and CD8+ T cells, as well as CD4+ and CD8+ Tm cells is associated with the final rejection. Furthermore, local CD4+ and CD8+ Tregs expressing Foxp3 and Helios are probably insufficient to impose the acceptance of CTX.