Rheumatic carditis: In vitro responses of peripheral blood leukocytes to heart and streptococcal antigens

Abstract

Cell-mediated immune responses to heart and streptococcal cell walls were studied in 21 children with rheumatic carditis and 15 clinically well children. The bioassay employed was proliferation of blood leukocytes, quantitated by in vitro tritiated thymidine incorporation. Neither the rheumatic children nor control subjects showed statistically significant leukocyte responses to heart homogenates or a purified myocardium fraction. In contrast, both groups of patients exhibited significant responses to streptococcal cell walls. The results suggest that patients with rheumatic carditis do not mount a cellular immune response to heart, as might be expected if cell-mediated autoimmunity is a feature of this disease.Group A streptococcal pharyngitis is a prerequisite for acute rheumatic carditis, but the events leading to the characteristic myocardial From the Samuel J.

T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

“…These T-cell clones predominantly recognized M5 peptides encompassing residues 81 to 103 (15 of 32 [46.9%]). Peptides M5(1-20), M5 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), and M5(163-177) were recognized by 3 of 32 (9.4%), 3 of 32 (9.4%), and 6 of 36 (16.7%) peptide-reactive heart-infiltrating T-cell clones, respectively (Fig. 1A).…”

“…Peptide M5(1-20) was recognized by PBMC from 35.1% of patients with severe RHD and those from 8.6% of controls, (P ϭ 0.01) ( Table 1). Peptides M5 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and M5(125-139) were predominantly recognized by PBMC from patients with mild RHD compared with controls (P ϭ 0.008 and P ϭ 0.01, respectively) ( Table 1). Although 54.5% of patients with mild RHD and 5.4% of patients with severe RHD presented Sydenham chorea (P Ͻ 0.001) we could not identify any specific antipeptide reactivity among these patients.…”

“…Molecular mimicry between streptococcal antigens, mainly the M protein, and heart tissue proteins is proposed as an important factor leading to the heart lesions found in RHD patients. Several studies have been performed with human peripheral blood mononuclear cells (PBMC) showing reactivity against the streptococcal cell wall and tissue antigens (20,25). CD4 ϩ T cells are the predominant population at the site of heart lesions (23, 16).…”