Toxoplasmic encephalitis occurs with inordinate frequency in patients with AIDS. This opportunistic infection occurs as a result of recrudescence of a latent infection whose cell mediated immune system has been compromised by infection with HIV. Toxoplasmic antigen has been shown to be both extremely potent stimulator of certain parameters of immune function and suppress other parameters. It has been demonstrated that activation of CD4 positive T-cells with mitogens is necessary for in vitro propagation of HIV. We hypothesize that because Toxoplasma is both chronically present and a potent stimulator of immune function, subclinical recrudescence of Toxoplasma infection will potentiate CD4 positive T-cells and possibly monocytes to be more permissive to HIV infection. In this study we will define the precursor frequency of T-helper cells to Toxoplasma antigen in HIV infected patients as compared to non-HIV infected controls and follow these patients prospectively for preferential loss of Toxopoplasma specific T-cells. We will assess by limiting dilution studies whether Toxoplasma antigen is a more efficient stimulator of T-cells and show that a greater proportion of T-cells are more permissive to HIV when stimulated with Toxoplasma antigen compared to other antigens. Furthermore, we will assess whether Toxoplasma antigen plays, a role in induction of CD4 on monocytes. Finally, we will directly investigate the role of toxoplasmic encephalitis in the development of HIV induced encephalitis by immunohistochemical techniques and in vitro hybridization. These studies may offer a rationale for early prophylactic treatment of all HIV patients who are seropositive for T. gondii.
Showing the most recent 10 out of 27 publications