Cellular Immune Responses to Recombinant Antigens in Pregnant Women Chronically Infected with Toxoplasma gondii

ABSTRACT

The parasite Toxoplasma gondii can infect most mammals and birds, sometimes causing severe pathology. Primary infection during pregnancy can result in abortion or fetal defects. Host immunity, particularly cellular immunity towards antigenic peptides, can control infection, but an efficient vaccine is not yet available. We have evaluated T-cell responses to a crude soluble toxoplasma antigen (ST-Ag) and to five recombinant peptide antigens of cells in whole-blood cultures from 22 pregnant women with preexisting infections and from 7 pregnant negative controls. Cells from all infected patients but from none of the controls responded specifically to ST-Ag by expressing surface CD25 on culture. Responses to the recombinant antigens showed considerable variation between individuals. rGRA1 elicited a response in 16 of the 22 samples (73%), rSAG1 in 13, rGRA7 in 9, rGRA6-CT in 4, and rGRA6-NT in only 1. Most responding cells were CD4⁺. Cells from infected subjects cultured with ST-Ag all released high levels of gamma interferon (IFN-γ) into the culture supernatant (4,343 ± 2,536 pg/ml). Cells from 12 patients released IFN-γ after culture with rGRA1 (130 ± 98 pg/ml), those from 10 patients released it after culture with rSAG1 (183 ± 128 pg/ml), and those from 4 patients released it after culture with rGRA7 (324 ± 374 pg/ml). Intensity of IFN-γ production in response to the latter two recombinant antigens correlated with responses to ST-Ag (r = 0.61 and 0.53, respectively; P < 0.01). Interleukin-4 was always absent from supernatants of cells stimulated with toxoplasma antigens. The heterogeneity of human responses to individual recombinant toxoplasma antigens should be considered in the design of potential vaccines.