TNFα-Signaling Modulates the Kinase Activity of Human Effector Treg and Regulates IL-17A Expression.

Maintenance of regulatory T cells CD4CD25FOXP3 (Treg) stability is vital for proper Treg function and controlling the immune equilibrium. Treg cells are heterogeneous and can reveal plasticity, exemplified by their potential to express IL-17A. TNFα-TNFR2 signaling controls IL-17A expression in conventional T cells via the anti-inflammatory ubiquitin-editing and kinase activity regulating enzyme A20 (tumor necrosis factor-alpha-induced protein 3).

TNF-α-induced protein 3 (TNFAIP3)/A20 acts as a master switch in TNF-α blockade-driven IL-17A expression.

Background: Anti-TNF inhibitors successfully improve the quality of life of patients with inflammatory disease. Unfortunately, not all patients respond to anti-TNF therapy, and some patients show paradoxical immune side effects, which are poorly understood. Surprisingly, anti-TNF agents were shown to promote IL-17A production with as yet unknown clinical implications.

KIR and Human Leukocyte Antigen Genotype Associated Risk of Cytomegalovirus Disease in Renal Transplant Patients.

Background: Cytomegalovirus(CMV) infections have a significant effect on morbidity and mortality in kidney transplants. We conducted a study to ascertain the association of natural killer cell killer immunoglobulin-like receptors and human leukocyte antigen (HLA) genotype with risk of CMV disease.

Methods: The 90 CMV-negative patients receiving a first renal transplantation from a CMV-positive donor in this study received triple immunosuppressive therapy and prophylactic CMV treatment for up to 3 months after transplantation.

Crosstalk between keratinocytes and T cells in a 3D microenvironment: a model to study inflammatory skin diseases.

The interaction between keratinocytes and immune cells plays a major role in the development of inflammatory skin diseases like psoriasis and atopic dermatitis. Pharmacological intervention to inhibit T cell-derived proinflammatory mediators is an effective therapy in the treatment of psoriasis. Here, we present a model to study the interaction between keratinocytes and T cells in a three-dimensional (3D) microenvironment, based on human skin equivalents populated with CD4+ T cells.

Human secondary lymphoid organs typically contain polyclonally-activated proliferating regulatory T cells.

Immunomodulating regulatory T-cell (Treg) therapy is a promising strategy in autoimmunity and transplantation. However, to achieve full clinical efficacy, better understanding of in vivo human Treg biology is warranted. Here, we demonstrate that in contrast to blood and bone marrow Tregs, which showed a resting phenotype, the majority of CD4(pos)CD25(pos)CD127(neg)FoxP3(pos) Tregs in secondary lymphoid organs were proliferating activated CD69(pos)CD45RA(neg) cells with a hyperdemethylated FOXP3 gene and a broad T-cell receptor-Vβ repertoire, implying polyclonal activation.

IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

In cancer patients pervasive systemic suppression of Dendritic Cell (DC) differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model.

KIR2DS5 is associated with leukemia free survival after HLA identical stem cell transplantation in chronic myeloid leukemia patients.

Background: Alloreactive NK cells play a role in tumor eradication after allogeneic HLA mismatched stem cell transplantation (SCT). The effect of NK alloreactivity in HLA identical SCT is still under debate and in particular in transplantation for chronic myeloid leukemia (CML) the data are very limited and with conflicting outcome. The aim of our study was to evaluate the effect of KIR genes and KIR ligands on leukemia free survival (LFS) and relapse rate in a well-defined, homogeneous group of CML patients phase upon HLA identical sibling SCT.

KIR gene and KIR ligand analysis to predict graft rejection after renal transplantation.

Background: The identification of transplant patients at high risk for rejection after reduction of immunosuppression would allow minimization of immunosuppression and avoidance of side effects in low-risk patients. Next to T cells, innate natural killer (NK) cells may contribute to graft rejection. NK cell activation depends on the balance between activating and inhibitory signals, delivered by self-human leukocyte antigens (HLA) through binding of killer-cell immunoglobulin receptors (KIR).

Reshaping the shared epitope hypothesis: HLA-associated risk for rheumatoid arthritis is encoded by amino acid substitutions at positions 67-74 of the HLA-DRB1 molecule.

Objective: To further analyze the association of HLA-DRB1 alleles with disease susceptibility in recent-onset rheumatoid arthritis (RA).

Methods: One hundred sixty-seven Caucasian RA patients and 166 healthy controls were typed for HLA-DRB1.

Results: The association of susceptibility to RA with the group of alleles encoding the shared epitope susceptibility sequences (SESSs) was confirmed in recent-onset RA.