A B S T R A C T The question of whether hypersensitivity to streptococcal antigens plays a role in the pathogenesis of the nonsuppurative sequelae of streptococcal infections remains at present unclear. As a first step in the approach to this question, the degree of cellular reactivity of peripheral blood leucocytes to streptococcal antigens was investigated in a number of rheumatic fever patients, patients with uncomplicated streptococcal infections, as well as normal healthy subjects.Using the in vitro technique for the inhibition of capillary migration of peripheral blood leucocytes as an index of the degree of sensitivity to streptococcal antigens, the results indicate that patients with acute rheumatic fever exhibit an exaggerated cellular reactivity to these antigens and in particular to streptococcal cell membrane antigens. This abnormal response to streptococcal membrane antigens appears to persist in rheumatic subjects for at least 5 yr after the initial 'attack of rheumatic fever. Only Group A streptococcal membrane antigens elicited this unusual response in rheumatic subjects, since the cellular reactivity to Group C and D streptococcal membranes was the same in all groups. Patients with evidence of valvular disease exhibited the same degree of cellular reactivity to these antigens as did patients without clinical evidence of rheumatic heart disease.The nature of the antigens responsible for the observed cellular response remains unknown. Enzymatic treatment of streptococcal cell walls and membranes designed to remove type-specific M proteins did not alter the observed cellular reactivity to the streptococcal antigens. The finding that an abnormal cellular response to certain streptococcal antigens is present only in rheuReceived for publication 17 July 1972 and in revised form 14 January 1974. matic patients suggests that cell-mediated factors may play an important role in the disease process.
INTRODUCTICNThe question of whether hypersensitivity to hemolytic streptococci and their products might play a role in the pathogenesis of the nonsuppurative sequelae of streptococcal infections has been the subject of investigation for many years. Starting with the early work of Swift and Derick and Derick, Hitchcock, and Swift in animals (1-3), it was apparent that delayed hypersensitivity to streptococci behaved in a manner similar to that observed for tuberculin sensitivity (4). Initiation of sensitivity by prolonged focal contact between the intact bacteria and tissues of the host, inability to passively transfer streptococcal-delayed hypersensitivity with serum alone, and the lack of correlation between circulating antibodies to streptococcal products and delayed allergy were all characteristics of the streptococcal hypersensitive state (5). Apropos of these studies, several intriguing observations concerning the streptococcal hypersensitive state were made. First, repeated small inoculations of heat-killed streptococci were more effective in inducing the hypersensitive state than a single inoculation of ...