Relative imbalance between T regulatory cells and activated T cells in mice with differential morbidity in chronic Schistosoma mansoni infections

Abstract

Chronic (20-week) Schistosoma mansoni infections of CBA/J male mice present as two distinct forms of morbidity. Most mice develop moderate splenomegaly syndrome (MSS) resembling the intestinal form of chronic human schistosomiasis mansoni, while approximately 20% of mice develop hypersplenomegaly syndrome (HSS), more consistent with the severe hepatosplenic form of chronic human schistosomiasis mansoni. Here, we report the relative proportions of natural T regulatory cells (Treg) and activated CD4(+) T cells (Tact) for both splenic and granulomatous cell populations of MSS and HSS mice. Proportions of both Treg and Tact are greater in HSS than MSS mice. However, the ratios of Treg to Tact in both splenic and granulomatous cell populations from MSS mice are significantly higher than those of HSS mice. For both HSS and MSS mice, in vitro proliferation of their CD3(+) splenic cells induced by soluble egg antigens is inversely correlated with the ratio of Treg to Tact. Also, spleen or granuloma cells from MSS mice produced higher mean levels of IFN-gamma than those from HSS mice. Differential IFN-gamma productive capacities dictated by Treg : Tact ratios may contribute to the development of differential morbidities in this model of chronic experimental schistosomiasis mansoni.

Strongyloides ratti Infection Induces Expansion of Foxp3+ Regulatory T Cells That Interfere with Immune Response and Parasite Clearance in BALB/c Mice

“…The central role of Tregs in the control of immune pathology in murine helminth infections is supported by several studies: S. mansoni-infected mice displayed increased liver pathology if Tregs were depleted or Treg expansion was restricted (11,20). Also, the development of severe hypersplenomegaly syndrome in chronic S. mansoni infection correlated to the ratio of Tregs/activated T cells (57). Trichuris muris isolates that induced a more pronounced Treg expansion upon infection displayed prolonged survival within their murine hosts.…”

Murine schistosomiasis as a model for human schistosomiasis mansoni: similarities and discrepancies

“…However, the ratios of Treg to Tact in MSS mice are significantly higher than those of HSS mice. It should be noted that the majority of mice develop MSS resembling the intestinal form of chronic human schistosomiasis, whereas only 20% of mice develop HSS that is more consistent with the severe hepatosplenic form of chronic human schistosomiasis mansoni (Watanabe et al 2009). In a study of S. mansoni-infected mice coinfected with murine AIDS (MAIDS), it was found that MAIDS did not influence the hepatic granulomatous reaction to S. mansoni in coinfected mice (Lacroix et al 1998).…”

“…It was reported that innate effectors and regulatory T cells producing IL-10 cooperate to reduce morbidity and prolong survival in schistosomiasis (Hesse et al 2004). Watanabe et al (2009) reported that the proportions of natural T regulatory cells (Treg) and activated CD4 + T cells (Tact) for both splenic and granulomatous cell populations are greater in mice with hypersplenomegaly syndrome (HSS) than those with moderate splenomegaly syndrome (MSS). However, the ratios of Treg to Tact in MSS mice are significantly higher than those of HSS mice.…”

T cells in helminth infection: the regulators and the regulated

“…For example, expanded and activated Foxp3 + Treg populations down-regulate Th2 responses towards the S. mansoni eggs that engender pathogenic reactions when trapped in tissue vasculature [25,38] and the severity of egg-induced liver pathology is negatively correlated with Foxp3 + Treg numbers [39]. The down-modulation of perioval granuloma 8 weeks post infection is associated with increased Foxp3 + Treg activation [25] and pathology can be alleviated by retroviral transfection of mice with Foxp3 [40] or transfer of infection-associated CD4 + CD25 + Tregs [41].…”