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Restricted heterogeneity of T cell receptor variable alpha chain transcripts in hearts of Chagas' disease
E Cunha-Neto1, R Moliterno, V Coelho
1Laboratory of Transplantation Immunology, São Paulo Heart Institute, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Insights
In Chagas
Area of Science:
- Immunology
- Cardiology
- Molecular Biology
Background:
- Autoimmunity's role in chronic Chagas' heart disease pathogenesis is debated.
- T cell infiltrates may drive heart damage in parasite-absent lesions.
- Understanding T cell receptor diversity is key to Chagas' cardiomyopathy mechanisms.
Purpose of the Study:
- To investigate T cell receptor (TCR) repertoire diversity in heart lesions of Chagas' cardiomyopathy patients.
- To compare the diversity of TCR V alpha and V beta subfamilies in affected heart tissue.
- To explore the implications of TCR repertoire restriction for autoimmunity in Chagas' disease.
Main Methods:
- Polymerase chain reaction (PCR) was used to amplify TCR V alpha and V beta subfamily sequences.
- Transcripts from heart samples of Chagas' cardiomyopathy patients were analyzed.
- TCR repertoire diversity was assessed by the number and prevalence of TCR V alpha and V beta subfamilies.
Main Results:
- A significantly narrower TCR V alpha repertoire (average 7.1 subfamilies) compared to TCR V beta repertoire (average 15.1 subfamilies) was observed in Chagas' heart lesions.
- TCR V alpha subfamilies were detected in fewer samples (39.6%) than TCR V beta subfamilies (73.5%).
- Normal heart tissue showed similar diversity for both TCR V alpha and V beta subfamilies in scarce T cells.
Conclusions:
- The restricted TCR V alpha repertoire in Chagas' heart lesions suggests a targeted autoimmune response.
- These findings support the hypothesis that T cells recognize limited heart-specific antigens in chronic Chagas' cardiomyopathy.
- The study provides evidence for a potential autoimmune mechanism driving heart damage in Chagas' disease.
Abstract:
The role of autoimmunity in the pathogenesis and progression of heart lesions in the chronic phase of Chagas' disease is controversial. In the absence of parasites in situ, the T cell infiltrate seen in heart lesions may be the primary determinant of tissue damage ultimately leading to heart failure and death. We used the polymerase chain reaction to amplify each known T cell receptor (TCR) V alpha and V beta subfamily-specific sequence in transcripts derived from heart samples obtained from Chagas' cardiomyopathy patients. The average number of TCR V alpha subfamilies (7.1 per tissue sample) was significantly lower than that for TCR V beta subfamilies (15.1 per sample). The average percentage of tissue samples positive per TCR V alpha and V beta subfamily was respectively 39.6% vs. 73.5%. These data suggest that, in Chagas' heart lesions, the detectable TCR V alpha repertoire is significantly narrower than TCR V beta repertoire. On the other hand, in normal heart tissue, diversity of V alpha and V beta TCR is similar among the scarce circulating T cell population. Such evidence of restricted TCR V region repertoire has been described in experimental and human autoimmune diseases. Our results are consistent with the possibility that T cells responsible for heart damage in chronic Chagas' cardiomyopathy may be recognizing a few heart-specific antigenic targets.