The response of lymphocytes from 17 patients with primary, secondary, and tertiary syphilis to phytohaemagglutinin (PHA) and to allogeneic lymphocytes was normal in heterologous serum; however, the responsiveness of cells from some patients with primary and secondary disease was significantly reduced in the presence of autologous serum. As cells from healthy controls invariably responded better to these stimuli in autologous serum, the sera from 81 patients with syphilis were screened for

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... suppressive properties. Sera from 25 primary, 32 secondary, two tertiary, six congenital, and 16 latent cases of syphilis were examined for their ability to reduce the responsiveness of normal cells to PHA. These experiments were performed with test sera as the sole source of serum for the cultures or with test sera added to cultures containing optimally supportive amounts of pooled human plasma. Stimulation of normal cells from one control in human plasma and 20%o test serum showed that only in sera from congenital cases of syphilis was the mean response significantly different from the response seen in control sera; a significant increase in the response to stimulation occurred. The range of response to PHA with sera from cases of primary and secondary syphilis was wider than with normal sera. Sera from five (20%) cases of primary and 14 (44%o) cases of secondary syphilis appeared to be immunosuppressive. When retested on another sample of normal cells, these sera were consistently immunosuppressive even in the presence of 15% pooled human plasma. Thus, in early syphilis antigenic stimulation may result in the release from suppressor cells of non-specific immunoregulators of cell-mediated immunity. Such phenomena may be a prelude to the development of tolerance to treponemal antigens. In congenital syphilis the development of suppressor cells may be impaired, resulting in the apparent immunostimulatory properties of serum from such cases.