Restriction in the usage of variable β regions in T-cells infiltrating valvular tissue from rheumatic heart disease patients

Rheumatic Heart Disease (RHD) is a delayed consequence of a pharyngeal infection with group A streptococcus (GAS), usually ascribed to a cross-reactive immune response to the host's cardiac tissues. Several GAS proteins have been reported to be superantigens, also raising the possibility that T cells in RHD could be driven by superantigens. We therefore analysed the variable beta (Vβ) repertoire of T cells infiltrating heart valves from chronic RHD patients undergoing elective valvular surgery. We analysed 15 valve specimens from patients with longstanding quiescent RHD and control valves from four non-rheumatic individuals. Total RNA was extracted from fresh valve tissue and employed to amplify 22 Vβ genes by RT-PCR. In valvular tissue, a restricted number of only 2 to 9 Vβ regions were detected as opposed to the findings in control valves. In 8 RHD valves, the expression of Vβ1, 2, 3, 5.1, 7, 8, 9 or 14 was marked. These Vβ regions have been related to GAS superantigens. Our results evidence the presence of a restricted set of T lymphocytes in valvular tissue from a majority of patients with chronic RHD and suggest that valvular sequelae in these patients might be related to a local antigen or superantigen driven inflammatory process that persists even many years after the initial triggering event.