concanavalin-a and Elephantiasis--Filarial

Reduced lymphocyte transformation to Wuchereria bancrofti microfilariae excretory-secretory antigen and Con A were observed in clinical filarial patients. Pre-incubation of normal human peripheral blood mononuclear cells with sera from filarial patients with clinical manifestations such as hydrocele and elephantiasis suppressed Con A induced responses. Effect of fractionated clinical filarial serum on Con A induced lymphocyte transformation showed that the inhibitory activity was associated with high molecular weight serum fraction.

Topics: Animals; Cells, Cultured; Concanavalin A; Elephantiasis, Filarial; Humans; Immune Tolerance; Lymphocyte Activation; Wuchereria bancrofti

Filarial parasites induce immune response in humans which are still poorly characterized. To define the antigens responsible for inducing lymphocyte responses, fast protein liquid chromatography was used to fractionate the antigens of Brugia malayi adult worms which were then tested on lymphocytes from patients with filariasis and normal controls. From an anion exchange column (Mono Q), three peaks of lymphocyte-stimulating activity were eluted which were further fractionated by gel filtration (Superose-12). Peak I induced both a proliferative response as well as the production of filaria-specific antibody in patient lymphocytes. Peak II, capable of inducing only a proliferative response (without antibody production) in patient lymphocytes, was a glycoprotein with phosphocholine as one of the antigenic determinants. Peak III induced proliferative responses in both patient and normal lymphocytes and thus appears to be mitogenic. Two-dimensional gel electrophoresis was then used to identify changes in the major cellular proteins associated with the activation of patient lymphocytes by these partially purified antigens. Stimulation of patient lymphocytes with peak I resulted in increased synthesis of immunoglobulin heavy, light, and J chains. Further, these were the only major secreted proteins found in the culture supernatants. Peak II resulted in quantitative changes in proteins associated with T and not B lymphocyte stimulation. Further analysis of these antigens should help to elucidate the mechanism of host-parasite interaction at both the cellular and molecular levels.

Topics: Animals; Antigens, Helminth; Brugia; Chromatography, Gel; Chromatography, High Pressure Liquid; Concanavalin A; Elephantiasis, Filarial; Epitopes; Humans; Lymphedema; Lymphocyte Activation

Inhibition of Concanavalin A-induced lymphocyte proliferation was used to monitor the partial purification and characterization of suppressor molecules from microfilariae of Brugia malayi. Suppressor activity was present in high molecular weight fractions of microfilarial extracts (Mr greater than 50 kd on SDS-PAGE) and was protease-sensitive but resisted treatment with sodium periodate, indicating that it is associated with parasite proteins. Suppressor activity was released by microfilariae cultured in vitro and could be detected in peritoneal exudates of intraperitoneally-infected jirds and in lymph and sera from athymic C3H/HeN mice with patent B. malayi infections. These findings indicate that immune unresponsiveness during patent filarial infections may result from the in vivo release by microfilariae of high molecular weight proteins that suppress host immune responses.

Topics: Animals; Brugia; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Elephantiasis, Filarial; Filariasis; Gerbillinae; Humans; Immune Tolerance; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred C3H; Microfilariae; Proteins

A concanavalin-A-induced suppressor cell assay was carried out in 10 patients with chronic filarial disease, 13 asymptomatic microfilaria carriers and 7 healthy subjects. Both the chronic filarial patients and the asymptomatic microfilaria carriers showed statistically significant reduced suppression indices when compared with the control subjects. The reduction in suppression indices was greater in the microfilaria carriers than in the chronic filarial patients.

Topics: Cells, Cultured; Concanavalin A; Dose-Response Relationship, Drug; Elephantiasis, Filarial; Humans; Immune Tolerance; Lymphedema; Lymphocyte Activation; Lymphocyte Cooperation; Lymphocytes; Suppressor Factors, Immunologic; T-Lymphocytes, Regulatory; Wuchereria bancrofti