RESTRICTED HETEROGENEITY OF T-CELL RECEPTOR VARIABLE ALPHA-CHAIN TRANSCRIPTS IN HEARTS OF CHAGAS-DISEASE CARDIOMYOPATHY PATIENTS

The role of autoimmunity in the pathogenesis and progression of heart lesions in the chronic phase of Chagas' disease is controversial. In t he absence of parasites in situ, the T cell infiltrate seen in heart l esions may be the primary determinant of tissue damage ultimately lend ing to heart failure and death. We used the polymerase chain reaction to amplify each known T cell receptor (TCR) V alpha and V beta subfami ly-specific sequence in transcripts derived from heart samples obtaine d from Chagas' cardiomyopathy patients. The average number of TCR V al pha subfamilies (7.1 per tissue sample) was significantly lower than t hat for TCR V beta subfamilies (15.1 per sample). The average percenta ge of tissue samples positive pet TCR V alpha and Y beta subfamily was respectively 39.6% vs. 73.5%. These data suggest that, in Chagas' hea rt lesions, the detectable TCR V alpha repertoile is significantly nar rower than TCR V beta repertoire. On the other hand, in normal heart t issue, diversity of V alpha and V beta TCR is similar among the scarce circulating T cell population. Such evidence of restricted TCR V regi on repertoire has been described in experimental and human autoimmune diseases. Our results ave consistent with the possibility that T cells responsible for heart damage in chronic Chagas' cardiomyopathy may be recognizing a few heart-specific antigenic tal gets.