Delayed‐type hypersensitivity induced in immunodeficient mice with syngeneic modified self antigens: a suggestive model of autoimmune response

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Abstract
Previous studies suggested that trinitrophenyl (TNP)‐modified syngeneic red cells induced humoral autoimmune response in mice with defective T cell function but not in normal mice. The ability of modified self antigen to induce autoimmune response in immunodeficient mice was further explored using the delayed‐type hypersensitivity (DTH) as an assay system. Mice were immunized with syngeneic TNP‐modified spleen cells (TNP‐SC) and challenged by syngeneic nonmodified conconavalin A (Con A) or lipopolysaccharide (LPS)‐stimulated spleen cells injected into their footpads. The DTH response was assessed 24, 48 and 72 h later by measuring the footpad swelling and was transferred to naive recipients with enriched T cells from TNP‐SC‐immunized irradiated A mice but not with serum or non‐T cells. Adult thymectomized, X‐irradiated (250 rds) and cyclophosphamide‐treated mice injected with syngeneic TNP‐SC generated a DTH response when subsequently challenged with syngeneic lymphoblasts (induced with Con A or LPS) but not when challenged with allogeneic blast cells. In contrast, normal mice treated in a similar manner exhibited a much less significant DTH response. SC incubated 1 to 3 h with Con A failed to elicit the DTH response of immunodeficient mice previously injected with TNP‐SC. Both lymphoblasts that were induced in vitro with Con A diluted in fetal calf serum or in normal mouse serum‐containing media, and lymphoblasts that were induced in vivo by interleukin 2 elicited DTH responses in X‐irradiated, TNP‐SC immunized mice. The syngeneic DTH response of the immunodeficient mice injected with TNP‐SC was abrogated when they were simultaneously transplanted with syngeneic SC or nylon wool‐passed syngeneic SC. If the transplanted splenocytes had been treated with anti‐Thy‐1 antiserum and complement they failed to abrogate the syngeneic‐DTH response of the above mentioned mice. This result suggests that suppressor cells are programmed to control the autoimmune response induced with modified self antigens.