Thymocyte-dependent immunity to toxoplasmosis in the normal and immunocompromised guinea-pig host

Abstract

Guinea-pigs made T-cell deficient by thymectomy and irradiation, and protected with syngeneic bone marrow cells (T.times.B) have a greatly reduced capacity to express normal cell-mediated immune functions, based on their poor responses to T-cell mitogens, prolonged acceptance of skin allografts, and susceptibility to the lethal effects of graft-versus-host disease. Further evidence for impaired T-cell activity in T.times.B guinea pigs was based on their inability to be fully sensitized to myobacterial antigens, and increased susceptibility to an intradermally induced infection with the intracellular protozoan parasite, Toxoplasma gondii (RH strain). After challenge at multiple sites with 106 or 105 parasites toxoplasmosis in thymus-intact, fully immunocomponent guinea pigs is a self-limiting and survivable infection, whereas the disease takes an acutely lethal course in the majority of T.times.B guinea-pigs. The latter also had more parasites disseminating to various tissues sites than their euthymic counterparts. The reduced capacity of T.times.B guinea-pigs to respond to mycobacterial products, and to generate anti-Toxoplasma immunity can be restored by an intravenous infusion of normal syngeneic thymocytes. These findings provide substantial direct evidence strenghthing the concept that protection against toxoplasmosis is heavily dependent upon an intact T-cell component of the host''s immune response.