Lymphatic filariasis is in many respects an immunological disease. Chronic lymphatic pathology and Tropical Pulmonary Eosinophilia, for example, are associated with cellular and humoral hyperresponsiveness, respectively. In contrast, patients with persistent microfilaremia are characteristically hyporesponsive to parasite antigens. In both human and animal models of infection, reduced in vitro responsiveness to parasite antigens is associated with the presence of suppressor cells and serum factors. The exact nature of these regulatory cells and factors and their mechanism of action have not been well defined. Furthermore, the impact of these immunoregulatory mechanisms on the expression of functional immune responses directed against microfilariae or infective larvae is unknown. In the present study, the Brugia pahangi-jird system will be employed to characterize antigen specific regulatory cells and factors as well as their mode of action. Suppressor cells will be characterized based on their reactivity with monoclonal antibodies, lectin binding properties, and with affinity chromatographic techniques. Serum factors will be purified by HPLC and characterized by their binding to parasite specific idiotype or anti-idiotype columns. The specificity of suppressor activity will be examined by studying the effects of purified regulatory cells or factors on the functional activation of T cell clones. Similarly, suppressor mechanisms will be analyzed by determining regulatory effects on IL-2 receptor expression. In vitro techniques will also be employed to analyze the regulation of B cell responses and to determine if parasite specific antibody responses are regulated in microfilaremic jirds. Mitogen and antigen stimulated cultures of normal or immune cells will be assayed for total and parasite specific immunoglobulin production. Culture supernatants will be analyzed by Western blot transfers in an attempt to demonstrate correlations between specific antigen recognition an immunologic and parasitologic status. Finally, the in vitro relevance of these observations will be addressed by analyzing the regulatory effects of cells or serum factors from infected donors on immunity to microfilariae or infective larvae in naive or immunized recipients. These studies should help define the relationship between immunoregulatory and resistance mechanisms and as such, represent an important correlate of efforts to induce immunity through vaccination.
| Leiva, L E; Lammie, P J (1989) Modulation of lymphocyte activation by soluble Brugia pahangi extracts. Trop Med Parasitol 40:327-31 |
| Leiva, L E; Lammie, P J (1989) Regulation of parasite antigen-induced T cell growth factor activity and proliferative responsiveness in Brugia pahangi-infected jirds. J Immunol 142:1304-9 |
| Prier, R C; Lammie, P J (1988) Differential regulation of in vitro humoral and cellular immune responsiveness in Brugia pahangi-infected jirds. Infect Immun 56:3052-7 |
| Michaud, L A; Lammie, P J (1988) Regulation of jird lymphocyte responsiveness to fractionated antigens of Brugia pahangi. Trop Med Parasitol 39:317-21 |
