Infectious Tolerance

Thymus requirement and antigen dependency in the "infectious" tolerance pathway in transplant recipients.

We have shown that features of infectious tolerance, as originally described in thymectomized mice, may be applied to euthymic rat recipients of heart transplants. We now report on studies aimed at exposing mechanisms underlying the infectious tolerance pathway, with emphasis on the role of thymus and alloantigen. Pretransplant thymectomy diminished the efficacy of CD4-targeted therapy, with do...

Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance.

Nondepleting anti-CD154 (CD40 ligand) mAbs have proven effective in inducing transplantation tolerance in rodents and primates. In the induction phase, anti-CD154 Ab therapy is known to enhance apoptosis of Ag reactive T cells. However, this may not be the sole explanation for tolerance, as we show in this study that tolerance is maintained through a dominant regulatory mechanism which, like to...

Impaired glucose tolerance in rat islet isograft recipients after cytomegalovirus infection.

Bone marrow transplantation induces either clonal deletion or infectious tolerance depending on the dose.

The concept of immunologic tolerance arose from bone marrow transplantation in neonatal or irradiated mice, in which the predominant mechanism is clonal deletion of donor-specific T cells by donor hemopoietic cells in the recipient thymus. A short term treatment with nonlytic CD4 and CD8 mAbs can induce tolerance to tissue allografts or reversal of spontaneous autoimmunity. Such tolerance to sk...

Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance

A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4(+)Foxp3(+) cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3(hCD2) mice to isolate and ablate Foxp3(+) T reg cells with an anti-hCD2 antibody, we show for the first time that CD4(+)Foxp3(+) cells are crucial for infectious tolerance induced by nonablative anti-...

Viral and Bacterial Infections Interfere with Peripheral Tolerance Induction and Activate CD8+ T Cells to Cause Immunopathology

We studied the impact of various infectious and proinflammatory agents on the induction of peripheral T cell tolerance. Adoptive transfer of CD8+ T cells from lymphocytic choriomeningitis virus (LCMV) T cell receptor transgenic mice into LCMV antigen transgenic mice expressing the LCMV glycoprotein epitope (gp) 33-41 under control of a major histocompatibility complex class I promoter led to ef...