The results of our previous work indicated that cell-mediated immune response, of importance in protection against Treponema pallidum, is distinctly inhibited at certain periods of syphilitic infection. Considering that cytokines, produced by Th1 lymphocytes, take part in this response and that their secretion may be regulated by cytokines of Th2 lymphocytes, we examined if, and in which stages of syphilis, such a regulation may exist. In this study we have examined the ability of cells to produce IL-2, IFN and TNF (Th1 or Th1 like cytokines) as well as IL-6 and IL-10 (Th2 or Th2 like cytokines). It was found that cells of syphilitic patients were able to produce IL-2, IFN, TNF, IL-10 and weakly IL-6 already in primary seronegative syphilis. At the same stage of syphilis, but seropositive, ability of Th1 lymphocytes to produce cytokines reached the highest values, whereas the cells producing IL-10 lost this ability. The cells producing IL-6 and MIF had the highest ability in secondary early syphilis. In this stage of syphilis again slightly increased the ability of cells to secrete IL-10, which reached the highest value in early latent syphilis. The growing ability to produce IL-6 and IL-10 was accompanied with a diminished production of IL-2, IFN and TNF nearly in all stages of syphilis. Only MIF, in contrast to other cytokines, was produced in late syphilis without distinct changes. The greatest suppression of Th1 lymphocytes to produce cytokines and cells to secretion of MIF was found in early latent syphilis when the level of IL-10 in cell culture supernates was the highest. High ability of Th2 lymphocytes to cytokines secretion in late syphilis and low ability of Th1 ones, which are very important for cell-mediated immune response, may be the reason for facilitating T. pallidum multiplication and development of latent stages of disease despite presence of immunologically competent cells.

In a previous paper (Metzger and Podwiinska, 1967) evidence was presented that the development of agglutinability which occurs in ageing suspensions of T. pallidum (Hardy andNell, 1955, 1957; Metzger and Podwinska, 1965) (2) Each batch of treponeme suspensions under (i), (ii), and (iii), prepared anew for every immunization week, was tested for virulence by injecting 01 ml. of the suspension containing 29 million organisms at each of four sites on the shaven back of a rabbit, and 0 5 ml., 299

The results of our previous work indicated that cell-mediated immune response, of importance in protection against Treponema pallidum, is distinctly inhibited at certain periods of syphilitic infection. Considering that cytokines, produced by Th1 lymphocytes, take part in this response and that their secretion may be regulated by cytokines of Th2 lymphocytes, we examined if, and in which stages of syphilis, such a regulation may exist. In this study we have examined the ability of cells to produce IL-2, IFN and TNF (Th1 or Th1 like cytokines) as well as IL-6 and IL-10 (Th2 or Th2 like cytokines). It was found that cells of syphilitic patients were able to produce IL-2, IFN, TNF, IL-10 and weakly IL-6 already in primary seronegative syphilis. At the same stage of syphilis, but seropositive, ability of Th1 lymphocytes to produce cytokines reached the highest values, whereas the cells producing IL-10 lost this ability. The cells producing IL-6 and MIF had the highest ability in secondary early syphilis. In this stage of syphilis again slightly increased the ability of cells to secrete IL-10, which reached the highest value in early latent syphilis. The growing ability to produce IL-6 and IL-10 was accompanied with a diminished production of IL-2, IFN and TNF nearly in all stages of syphilis. Only MIF, in contrast to other cytokines, was produced in late syphilis without distinct changes. The greatest suppression of Th1 lymphocytes to produce cytokines and cells to secretion of MIF was found in early latent syphilis when the level of IL-10 in cell culture supernates was the highest. High ability of Th2 lymphocytes to cytokines secretion in late syphilis and low ability of Th1 ones, which are very important for cell-mediated immune response, may be the reason for facilitating T. pallidum multiplication and development of latent stages of disease despite presence of immunologically competent cells.

Among lectins from Lotus tetragonolobus, Ulex europaeus I and Evonymus europaea, agglutinating cells with blood group H determinants containing L-fucose alpha 1 leads to 2-linked to subterminal D-galactose, only the last lectin agglutinates thioglycolate- and paraffin oil-stimulated murine and guinea pig peritoneal exudate cells (PEC). The agglutination is inhibited by specific inhibitors of Evonymus lectin only: lacto-N-fucopentaose I and lactose. These results suggest the presence of a determinant on the surface of PEC, containing L-fucose alpha 1-linked at the nonreducing end which is different from blood group H determinants. Nonstimulated murine peritoneal cells (PC) are not agglutinated by the lectin but become agglutinable after neuraminidase treatment. Unstimulated guinea pig PC from different animals are agglutinated to a different extent by the same lectin concentration and show increased agglutinability after neuraminidase digestion. These results show that receptor for Evonymus lectin also exists on the nonstimulated PC but access to it is hindered by sialic acid. Trypsin- and pronase-digested PEC show increased agglutinability with Evonymus lectin. These results suggest that the lectin receptor is a glycolipid. Since alpha-linked L-fucose has been suggested as a part of the macrophage receptor for migration inhibitory factor in the guinea pig (Remold, J. Exp. Med. 1973. 138: 1065), the effect of Evonymus europaea lectin on the migration of PEC was studied. It was found that lectin inhibits the migration of PEC in the capillary tube assay up to 80%.