T regulatory cell levels decrease in people infected with Schistosoma mansoni on effective treatment

Abstract

Schistosomiasis mansoni is usually a chronic infection that leads to long-term, systemic exposure to schistosome antigens. Experimental Schistosoma mansoni infection is associated with immunoregulatory mechanisms, including T regulatory cells (Treg) that may help control morbidity and dampen resistance to re-infection. We now show that some schistosomiasis mansoni patients have high proportions of CD3(+)/CD4(+)/CD25(high) Treg. On effective treatment with praziquantel, these high Treg percentages decrease, and fewer of the remaining Treg express CD45RO. The proportion of Treg in S. mansoni-infected patients is inversely related to their percentage of activated, putative effector T cells (CD3(+)/CD4(+)/CD25(medium)/HLA-DR(+) cells). We conclude some, but not all, schistosomiasis mansoni patients develop high percentages of circulating Treg, and effective treatment both decreases the levels of these cells and changes their phenotypes, possibly because of the removal of constant exposure to antigens from intravascular, egg-producing adult worms.

Figure 1

Flow cytometry analysis of whole blood cells stained with anti-CD3, anti-CD4, and anti-CD25 was used to define CD3⁺CD4⁺CD25^high cells. A, CD3⁺/CD4⁺ lymphocytes were gated and analyzed for positive CD25 expression using a threshold (B) based on the fluorescence minus one (FMO) “no CD25-PE” controls. After examination of the scatter plots of all patients, a threshold was set between CD25^medium and CD25^high cells [dotted line in A]. This threshold, and that provided by the FMO controls, was then used throughout for all analyses. C, Histogram of CD25-PE spectrum showing where the CD25^high gate was set throughout.

Figure 2

Percentages of Treg (CD3⁺CD4⁺CD25^high cells) in the peripheral blood of untreated, schistosome-infected patients. Horizontal dashed bars indicate stratification levels of patients with < 5%, 5%–10%, or > 10% Treg in their circulation.

Figure 3

Changes in levels of Treg and Treg subsets in 12 patients before treatment and after treatment and cure: (A) Treg; (B) PD-1 expression by Treg; (C) CD45RO expression by Treg.

Figure 4

No relationship between Treg percentages and infection intensities. Eggs per gram of feces (EPG) of untreated, HIV-1-negative patients compared with their percentage of Treg.

Figure 5

Inverse relationship of Treg and activated, putative effector T cells (CD4⁺CD25^mediumHLA-DR⁺ cells) in the peripheral blood of untreated, HIV-1 seronegative, schistosome-infected patients.