Protection of nude rats against Toxoplasma infection by excreted-secreted antigen-specific helper T cells

Abstract

In the present work we demonstrate the implication of excreted-secreted antigens in eliciting the protective cell-mediated immunity developed by rats toward Toxoplasma gondii. We first showed that 104 specific T cells from T. gondii-infected rats conferred to nude rats the ability to resist an infection by the highly virulent RH strain of T. gondii. In a second series of experiments, the role of excreted-secreted antigens in this protection was demonstrated. After the adoptive transfer to nude rats of various doses (103, 104, 105) of excreted-secreted antigen-specific helper T cells (propagated in vitro during one month), significant protection toward T. gondii was induced. Moreover, these cells were responsible for a specific antibody response in nude rats, which are normally unable to develop any specific humoral response. The specificity of these antibodies was directed toward different molecules with molecular masses of 104, 97, 57, 39, 30, 21, and 18 kilodaltons; some of these have been previously characterized as major excreted-secreted antigens.

Passive immunization protects guinea pigs from lethal toxoplasma infection

“…This finding, together with the evidence that the onset of acquired resistance was associated with generation in the peripheral lymphoid organs of T cells and B cells that were capable of adoptively immunizing normal guinea pigs against lethal T. gondii infection, correlates well with the hypothesis that cell-mediated immunity is a crucial host-defense mechanism against toxoplasmosis [5,6]. While the involvement of T cell-mediated effector mechanisms in immunity to this disease has been reasonably well established [2,4], there is less con-vincing evidence for ascribing an important role for B cells or their products (antibodies) in affording protection against T. gondii infection. In this regard, earlier studies [13,16] showed that passive immunization with homologous or heterologous serum containing polyclonal anti-Toxoplasma antibodies conferred little or no protection to recipient mice against virulent parasite challenge, nor does passive transfer of antibody to infected T cell-deficient mice promote their survival [16,17].…”

“…Such divergent results suggest that the choice of a suitable host species as well as selecting a particular parasite strain may be critical factors when performing passive protection studies and for drawing conclusions about the hostparasite relationship associated with toxoplasmosis. Interestingly, in this regard, the only other reported successful adoptive cell transfer systems for analyzing Toxoplasma immunity were found to occur in hamsters [18] or in rats [4].…”

“…With the use of appropriate animal models and passive transfer systems, past studies [1][2][3][4] have shown that acquired resistance to infection with the RH strain of Toxoplasma gondii depends upon activation of both humoral and cellular components of the host's immune system. In this regard, while there is convincing evidence for the T cell-mediated nature of anti-Toxoplasma immunity [2,3,5,6] there is now mounting evidence that antibodies or other humorat factors [1,2,7] are also protective against toxoplasmosis.…”

Protective immunity in the rat model of congenital toxoplasmosis and the potential of excreted‐secreted antigens as vaccine components

“…ESA have been shown to be protective in the models of acute infection of mice by direct immunization (Darcy et al 1992b). Their protective role has also been shown in nude rats passively transferred with serum or T cells from infected or ESA-immunized, euthymic rats , Ridel et al 1988, Duquesne et al 1990.…”

“…Several Toxoplasma antigens, such as the major immunodominant surface antigen SAG1 (Büllow & Boothroyd 1991, Khan et al 1991, Darcy et al 1992a) and excreted-secreted antigens (ESA), have been identified as potential vaccine candidates. In our laboratory, we have reported that ESA confer a significant protection against a lethal challenge with the 76K strain cysts in both mice, by direct immunization, and nude rats, by the passive transfer of immune sera or T cells , Duquesne et al 1990.…”