Restricted heterogeneity of T cell receptor variable alpha chain transcripts in hearts of Chagas’disease cardiomyopathy patients

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.