Infection with a virus generates a polyclonal immune response with broad alloreactive potential.

Virus-specific T cells have been shown to cross-react with allogeneic HLA (allo-HLA) at a clonal level. However, the impact of a single virus on the allorepertoire has never been investigated at the polyclonal level. We made an inventory of the incidence and specificity of allo-HLA-cross-reactive-virus-specific CD8 T cells in 24 healthy individuals.

Cross-Reactivity of Virus-Specific CD8+ T Cells Against Allogeneic HLA-C: Possible Implications for Pregnancy Outcome.

Heterologous immunity of virus-specific T cells poses a potential barrier to transplantation tolerance. Cross-reactivity to HLA-A and -B molecules has broadly been described, whereas responses to allo-HLA-C have remained ill defined. In contrast to the transplant setting, HLA-C is the only polymorphic HLA molecule expressed by extravillous trophoblasts at the maternal-fetal interface during pregnancy.

The avidity of cross-reactive virus-specific T cells for their viral and allogeneic epitopes is variable and depends on epitope expression.

Virus-specific T cells can recognize allogeneic HLA (allo-HLA) through cross-reactivity of their T-cell receptor (TCR). In a transplantation setting, such allo-HLA cross-reactivity may contribute to harmful immune responses towards the allograft, provided that the cross-reactive T cells get sufficiently activated upon recognition of the allo-HLA. An important determinant of T-cell activation is TCR avidity, which to date, has remained largely unexplored for allo-HLA-cross-reactive virus-specific T cells.

Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study.

Despite excellent short-term results, long-term survival of transplanted kidneys has not improved accordingly. Although alloimmune responses and calcineurin inhibitor-related nephrotoxicity have been identified as main drivers of fibrosis, no effective treatment options have emerged. In this perspective, mesenchymal stromal cells (MSCs) are an interesting candidate because of their immunosuppressive and regenerative properties.

Differential effect of pretransplant blood transfusions on immune effector and regulatory compartments in HLA-sensitized and nonsensitized recipients.

Background: Blood transfusion (BT) may elicit both harmful and beneficial immune responses against a subsequent organ graft. Immune parameters of a single, non leukocyte-depleted BT were investigated in two groups: non-human leukocyte antigen (HLA)-sensitized recipients with a one-HLA-DR matched donor (protocolled BT [PBT]) and females with previous exposure to HLA alloantigens through pregnancy (donor-specific transfusion [DST]).

Methods: Thirty-five percent of DST recipients and 9.

Differentially modulated dendritic cells induce regulatory T cells with different characteristics.

Dexamethason (DEX) treated DC display several features that establish them as candidates for specific allogeneic tolerance induction. We report the results of in vitro studies of polarization of the alloimmune T cell response with two types of differentially modulated human DC. Both DEX treated DC triggered by LPS for 6 h (DEX6-DC) and DEX treated DC triggered by LPS for 48 h (DEX48-DC) acquired low levels of costimulatory, adhesion, and MHC class II molecules compared with mature DC (mDC).

The ratio of interferon-gamma and interleukin-10 producing donor-specific cells as an in vitro monitoring tool for renal transplant patients.

If in vitro tools can be used to predict which renal transplant patients are at risk for rejection and which patients are more predisposed to tolerance, the immunosuppressive regimen can be adjusted to prevent rejection before it becomes clinically apparent or, in case of a tolerant patient, medication can be reduced or even stopped. Peripheral blood mononuclear cells (PBMC) of patients with persistent stable graft function and of patients with (biopsy-confirmed) acute rejection were stimulated with donor cells and tested with Elispot analysis. A significantly higher number of donor-specific interferon (IFN)-gamma producing cells were found in patients with rejection, as determined with Elispot analysis.

No in vitro evidence for a decreased alloreactivity toward noninherited maternal HLA antigens in healthy individuals.

Pre- and/or perinatal exposure to noninherited maternal HLA antigens (NIMA) is associated with a decreased HLA antibody formation against the NIMA and a significantly better graft survival of kidney grafts from siblings or those from unrelated donors who were mismatched for the NIMA haplotype compared with the NIPA (noninherited paternal HLA antigens) haplotype later in life. These observations suggest that some form of immunological tolerance against NIMA is induced. We analyzed the in vitro T cell reactivity of healthy individuals toward their parents and/or siblings expressing the NIMA or NIPA haplotype to explore whether the alloimmune response to NIMA has distinct characteristics compared with NIPA.

Prolongation of skin graft survival by modulation of the alloimmune response with alternatively activated dendritic cells.

Background: Activation of immature dendritic cells (DC) in the presence of the glucocorticoid hormone dexamethasone (DEX) results in alternatively matured DC that present antigen in the absence of a proper co-stimulatory context. This maturation process is irreversible, making these cells an attractive potential tool for the induction of antigen-specific T-cell tolerance in vivo. The authors explored the possibility of using these DC for the induction of transplantation tolerance in a fully allogeneic setting in mice.