Functional Studies of T Regulatory Lymphocytes in Human Schistosomiasis in Western Kenya

Abstract

Abstract.Immunoregulation is considered a common feature of Schistosoma mansoni infections, and elevated levels of T regulatory (Treg) lymphocytes have been reported during chronic human schistosomiasis. We now report that the removal of Treg (CD4+/CD25hi/CD127low lymphocytes) from peripheral blood mononuclear cells (PBMCs) of S. mansoni–infected individuals leads to increased levels of phytohemagglutinin (PHA)-stimulated interferon gamma (IFNγ) production and decreased interleukin-10 (IL-10) responses. Exposure to schistosome antigens did not result in measurable IFNγ by either PBMC or Treg-depleted populations. Interleukin-10 responses to soluble egg antigens (SEA) by PBMC were unchanged by Treg depletion, but the depletion of Treg greatly decreased IL-10 production to soluble worm antigenic preparation (SWAP). Proliferative responses to PHA increased upon Treg removal, but responses to SEA or SWAP did not, unless only initially low responders were evaluated. Addition of anti-IL-10 increased PBMC proliferative responses to either SEA or SWAP, but did not alter responses by Treg-depleted cells. Blockade by anti-transforming growth factor-beta (TGF-β) increased SEA but not SWAP proliferative responses by PBMC, whereas anti-TGF-β increased both SEA- and SWAP-stimulated responses by Treg-depleted cultures. Addition of both anti-IL-10 and anti-TGF-β to PBMC or Treg-depleted populations increased proliferation of both populations to either SEA or SWAP. These studies demonstrate that Treg appear to produce much of the antigen-stimulated IL-10, but other cell types or subsets of Treg may produce much of the TGF-β. The elevated levels of Treg seen in chronic schistosomiasis appear functional and involve IL-10 and TGF-β in antigen-specific immunoregulation perhaps leading to regulation of immunopathology and/or possibly decreased immunoprotective responses.

ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica

“…20,21,51,52 Treg cells play a pivotal role in limiting hepatic immunopathological damage in schistosomiasis. 22,23,51 In this study, our results showed that ApoE deficiency caused higher levels of TC and TG in mice, which is consistent with the previous studies that ApoE-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides. 53 It is widely recognized that ApoE is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins.…”

“…[47][48][49][50] Additionally, numerous studies have proved that the imbalance of Th17/Treg plays a pathogenic role during the development of schistosomiasis. [20][21][22][23]50,51 Our results showed that S japonicum infection up-regulated the frequencies of both hepatic Th17 and Treg in the ApoE −/− and WT mice.…”

“…Previous studies showed that Th17 and Treg orchestrate the development of liver pathology in schistosomiasis [20][21][22][23] ; we investigated F I G U R E 1 Schistosoma japonicum infection attenuated body weight while increased ratio of liver weight to its body weight (Hepatic mass index, HMI). At the 8th week after infection, the infected mice were sacrificed and the liver and body weight of each mouse was weighed (A) and the proportion of the liver weight to its body weigh was calculated and recorded as HMI (B).…”

“…Those results were consistent with the flow cytometric results. As the balance of Th17/Treg has proved to play critical roles in regulating the development of immunopathology in schistosomiasis, [20][21][22][23] we further calculated the ratios of Th17 to…”

Schistosoma “Eggs-Iting” the Host: Granuloma Formation and Egg Excretion

“…Regulatory T cells expand during the chronic stage of S. mansoni murine infection and are present in S. mansoni infected patients ( 127 – 129 ). It has speculated that immunosuppression by Treg cell by the release of IL-10 and TGFβ may limit tissue pathology toward trapped eggs during infection ( 130 – 132 ).…”