In Vivo and In Vitro Studies of Delayed-Type Hypersensitivity to Toxoplasma gondii in Guinea Pigs

Abstract

Delayed-type hypersensitivity develops late in the course of human toxoplasmosis, and a positive skin test is of some value for implicating chronic or eliminating acute forms of toxoplasmosis as a cause of disease. Toxoplasma-infected guinea pigs were studied to determine the onset and development of delayed-type hypersensitivity. Both the toxoplasmin skin test and the in vitro macrophage migration inhibition technique indicated that delayed hypersensitivity to toxoplasma antigen existed as early as 1 week after infection. The mechanism responsible for the observed inhibition of macrophage migration in vitro appeared to be an inhibitory factor(s) released from sensitized lymphoid cells in the presence of antigen.

In Vitro Induction of Nonspecific Resistance in Macrophages by Specifically Sensitized Lymphocytes

“…The Toxoplasma rnodel used in our studies should afford an ideal situation since, unlike the Listeria or Mycobacterium model in which resistance either results in the complete elimination of the organism from the tissues (5,14) or effectively sequesters it and renders it antigenically ineffective (6), a host infected with Toxoplasma remains infected for life, and there is ample evidence for continued antigenic stimulation throughout the life of the host (16,(20)(21)(22). Delayed hypersensitivity is acquired in guinea pigs within 1 week after Toxoplasma infection as measured by in vivo and in vitro techniques (10).…”

“…Migration inhibitory factor. The supernatant fluid media collected from the different groups of Leighton tubes were centrifuged at 10,000 X g to remove cellular debris and tested for their ability to cause inhibition of migration of normal guinea pig peritoneal exudate cells by using methods described previously (10).…”

Effect of Antithymocyte Serum on Experimental Toxoplasmosis in Mice

“…G. Huldt (Ph.D. thesis, Tryckeri Balder AB, Stockholm, 1967) has proposed that interferon might be responsible for the U) af early development of immunity to Toxoplasma; interferon has been shown to protect cells from Toxoplasma infection (14). However, an early development of cell-mediated immunity is indicated by the results of Krahenbuhl et al (9), who found positive delayed-hypersensitivity skin tests and positive macrophage migration-inhibition tests as early as 1 week after infection in Toxoplasma-infected guinea pigs. In view of the depressive effect of ATS on cell-mediated immunity (16) and the importance of such immunity in toxoplasmosis (5), the influence of ATS on the infection observed in the present experiments seems to be best explained by this effect.…”

Murine spleen and lymph node cellular composition and function during cyclophosphamide and splenectomy induced resistance to Toxoplasma gondii

“…Toxoplasma infection in mice and in humans has been associated with transient immune dysfunction manifest as reduced delayed hypersensitivity (DTH) responses (Jones 1980, Krahenbuhl & Remington 1982, varying degrees of in vitro proliferative responses to toxoplasma antigen in the first months after the illness (Anderson et al 1981 Krahenbuhl et al 1971, Maddison et at. 1979 and, in some patients and animal models, delayed appearance of lymphokines which activate mononuclear cells to inhibit toxoplasma (Johnson 198 1, Jones et al 1977).…”