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Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. II. Partial
F Y Liew1, J A Schmidt, D S Liu
1Department of Experimental Immunobiology, Wellcome Research Laboratories, Beckenham, UK.
Abstract:
Culture supernatants of splenic T cells from susceptible CBA mice chronically infected with Trypanosoma cruzi contain a suppressive substance which can inhibit the induction of delayed-type hypersensitivity (DTH) to a wide range of antigens. The suppressive substance is distinct from T. cruzi antigen inasmuch as the supernatant depleted of any residual T. cruzi antigen by an affinity column still retains the suppressive activity, whereas addition of T. cruzi antigens to control supernatant did not confer suppressive function. The suppressive supernatant does not contain detectable levels of IL-1, IL-2, IL-3, or IFN-gamma but a modest level of IL-1 and IL-2 inhibitory activities. However, both these inhibitory activities elute at a different position from the DTH suppressive activity on gel filtration. The DTH suppressive activity is heat labile (1 h, 56 degrees C), cryostable, but destroyed by trypsin treatment. It binds to ricin but not to lentil lectin. Sepharose 4B gel filtration and HPLC analysis in mild chaotropic agents (urea, ethylene glycol) demonstrate that the suppressive substance has an apparent Mr of 30 to 60 kDa, but full DTH-suppressive activity is retained only in an aggregated form.
Insights
A substance from T. cruzi infected mice suppresses immune responses, specifically delayed-type hypersensitivity (DTH). This immune suppression is distinct from the parasite itself and involves a heat-labile, trypsin-sensitive molecule.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Chronic Trypanosoma cruzi infection in mice leads to immune suppression.
- Splenic T cells from infected mice produce a substance that inhibits immune responses.
Purpose of the Study:
- To characterize the suppressive substance inhibiting delayed-type hypersensitivity (DTH) in Trypanosoma cruzi infected mice.
- To differentiate the suppressive substance from parasite antigens and other cytokines.
Main Methods:
- Affinity chromatography to remove parasite antigens.
- Gel filtration and HPLC for molecular weight determination.
- Assays for heat lability, cryostability, and sensitivity to trypsin and lectins.
Main Results:
- The suppressive substance is distinct from T. cruzi antigens and does not contain significant levels of IL-1, IL-2, IL-3, or IFN-gamma.
- The substance exhibits modest inhibitory activity against IL-1 and IL-2, but this differs from the primary DTH suppressive activity.
- The suppressive activity is heat labile, trypsin-sensitive, binds to ricin, and has an apparent molecular weight of 30-60 kDa, with full activity in an aggregated form.
Conclusions:
- A novel suppressive substance, distinct from parasite antigens, mediates immune suppression in chronic T. cruzi infection.
- This molecule plays a role in inhibiting delayed-type hypersensitivity (DTH) responses.
- Further characterization of this substance could reveal new therapeutic targets for Chagas disease.