Adoptive transfer of immunity to Treponema pallidum Nichols infection in inbred strain 2 and C4D guinea pigs

Abstract

T lymphocytes purified from lymph nodes and spleens of chancre-immune, inbred strain 2 guinea pigs, when infused into syngeneic guinea pigs, conferred protection against challenge with Treponema pallidum subsp. pallidum Nichols. No protection was conferred by similar injections of cell suspensions from normal guinea pigs or guinea pigs immunized with T. phagedenis biotype Reiter or T. pallidum-free testis supernatants from infected rabbits. Similar results were obtained with homozygous C4D guinea pigs. After several months of infection, 2 of 11 strain 2 and 1 of 8 strain C4D recipients of T. pallidum-immune cells developed an erythematous reaction of short duration at the injection site; 2 of these recipients were positive for T. pallidum. Throughout the experimental period the humoral response to treponemal antigens was substantially lower in the adoptively immune guinea pigs than in various unprotected control groups. Passive immunity to infection with T. pallidum, however, seems to be dose related, since asymptomatic infection persisted for as long as 3 months after challenge in strain 2 guinea pigs transfused with 10(8) T. pallidum-immune lymphocytes, but not in C4D recipients of twice as many immune cells.

Cytokine gene expression in skin of susceptible guinea‐pig infected with Treponema pallidum

“…In conclusion, in syphilis infection, the early and profuse humoral response, 31 the delayed acquisition of resistance to reinfection 2 and the protracted and incomplete elimination of the pathogen from the site of inoculation and distant organs 6,32 are all consistent with an early switch to an ineffective Th2 response.…”

“…Both hind legs of experimental and control guinea‐pigs were closely clipped and thoroughly disinfected. To prevent cross‐contamination, individual sets of sterile blades and forceps were used to dissect ≈10 mm 2 of the inoculated skin site in both hind legs. Similar specimens were collected from the unmanipulated animals.…”

“…It is known that resistance to reinfection with virulent Treponema pallidum (VTP) is a T‐cell mediated process. 1,2 Also known is the fact that acquisition of immunity in syphilis is a lengthy and deficient process. 2,3 The pathogen is not fully eradicated, allowing the occurrence of secondary and tertiary stages of reactivation in a substantial number of untreated individuals.…”

“…We have shown that the guinea‐pig is a suitable host for studies of experimental syphilis, 7,8 and delineation of mechanisms of immunity. 2 There are several strains of guinea‐pig displaying different susceptibilities to cutaneous inoculation with VTP. The Albany (Alb), a subline of Hartley strain is resistant [median infective dose (ID 50 )>10 9 organisms], whereas the C4‐deficient (C4D) strain is highly susceptible (ID 50 =10 2 organisms).…”

Effect of passive immunization with purified specific or cross-reacting immunoglobulin G antibodies against Treponema pallidum on the course of infection in guinea pigs

“…Adoptive transfer experiments indicated that the cellular arm of the immune response plays an important role in the acquisition of resistance against T. pallidum (for references, see reference 29). However, some animals infused with relatively large numbers of treponemal immune T lymphocytes (9,29) developed asymptomatic infections, suggesting that additional factors, possibly of a humoral nature, are required to effect full protection. It has been demonstrated that immune serum enhances the phagocytosis of treponemes by macrophages (1,16) and inhibits in vitro the attachment of the pathogen to mammalian cells (10) and to extracellular matrix components (11).…”