Related Experiment Videos
Trypanosoma cruzi-sensitized T-lymphocyte mediated 51CR release from human heart cells in Chagas' disease
Insights
T-lymphocytes from Chagas
Area of Science:
- Immunology
- Infectious Diseases
- Cardiology
Background:
- Chagas' disease, caused by Trypanosoma cruzi, can lead to cardiac complications.
- The role of autoimmune mechanisms in Chagas' disease pathogenesis is under investigation.
Purpose of the Study:
- To investigate the cytotoxic effects of T-lymphocytes from Chagas' disease patients on human heart cells.
- To explore the potential autoimmune basis of cardiac damage in Chagas' disease.
Main Methods:
- Human heart cells labeled with 51Cr were incubated with T-lymphocytes from patients with acute or chronic Chagas' disease and healthy donors.
- Cytotoxicity was measured by the release of 51Cr.
- Migration inhibition assays were performed using a heart cell antigen and Trypanosoma cruzi-immune leukocytes.
Main Results:
- T-lymphocytes from both acute and chronic Chagas' disease patients exhibited significant cytotoxicity towards human heart cells compared to controls.
- The highest cytotoxicity was observed with T-lymphocytes from patients with acute Chagas' disease.
- A heart cell antigen inhibited the migration of T. cruzi-immune leukocytes, suggesting cross-reactivity.
Conclusions:
- T-lymphocytes from Chagas' disease patients can be activated by cross-reactive heart cell antigens, indicating an autoimmune mechanism.
- This autoimmune response, mediated by T. cruzi-sensitized T-lymphocytes via delayed-type hypersensitivity, likely contributes to heart cell destruction in Chagas' disease.
Abstract:
Cytotoxicity of T-lymphocytes from patients with Chagas' disease to parasitized and non-parasitized human heart cells labelled with 51Cr was demonstrated. The highest ratio of 51Cr released from the normal, non-parasitized heart cells was observed when the T-lymphocytes were collected from patients with acute Chagas' disease. The quantity of 51Cr released from the normal heart cells that were destroyed by T-lymphocytes collected from patients with chronic Chagas' disease was also significantly higher than the quantity of 51Cr released from normal heart cells incubated with lymphocytes from normal donors. The specific release of 51Cr from the heart cell cultures destroyed by the immune T-lymphocytes from patients with acute Chagas' disease and from patients with chronic disease was 38.1% and 25.8%, respectively, compared to the release of 51Cr observed in control studies. A small particle human heart cell antigen was shown to inhibit the migration of Trypanosoma cruzi-immune peripheral blood leukocytes. The findings appear to indicate that T-lymphocytes from patients with Chagas' disease are susceptible to activation by a cross-reactive heart cell antigen and suggest that an autoimmune mechanism can be established in some cases of acute Chagas' disease and can be perpetuated in the chronic phase of this disease by the continuous antigenic stimulation. Further, these experimental data indicate that the autoimmune destruction of heart cells in Chagas' disease is produced by delayed-type hypersensitivity mediated by T. cruzi-sensitized T-lymphocytes.