The renaissance of the trans-vivo delayed-type hypersensitivity (DTH) assay.
In 2000, Orosz and colleagues published a seminal paper using a trans-vivo delayed-type hypersensitivity (DTH) assay to investigate the immunological basis of human allograft acceptance (1). Donor-specific DTH responses, elicited by the indirect pathway of alloantigen presentation, were measured after injection of recipient peripheral blood mononuclear cells (PBMCs) and donor-cell lysate into the footpad of severe combined immunodeficient (SCID) mice. PBMCs from rejecting individuals triggered strong swelling reactions associated with humancell retention and mouse neutrophil recruitment whereas PBMCs from clinically tolerant recipients induced reduced or no DTH responses. PBMCs from tolerant recipients retained normal DTH responses to recall antigens such as tetanus/diphtheria toxoid or Epstein–Barr virus, but these responses were suppressed in a TGFb- and IL-10-dependent manner when donor and third-party antigens were co-injected. The demonstration that allograft acceptance was associated with reduced donor-specific DTH responses and also with increased linked-suppression provided evidence that immune regulation was an important mechanism for renal allograft acceptance in humans (read more)
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