CD4⁺ and CD8⁺ Distribution Profile in Individuals Infected by Schistosoma mansoni

Abstract

Rationale: Patients with chronic Schistosoma mansoni infection show lower anti‐soluble egg antigen (SEA) proliferation responses and higher responses to soluble worm antigen preparation (SWAP). Objective: To compare the activation status and proliferation response of peripheral blood mononuclear cells (PBMC) of infected (XTO) and egg‐negative individuals (NI) living in the same endemic area. Methods: XTO (n = 51) and NI individuals from the same geographical area (n = 37) and healthy blood donors (n = 22) were evaluated before and after stimulation with SEA and SWAP. The expression of activation markers (CD4+ HLADR+, CD8high+HLA‐DR+ and CD8+ CD28+) and proliferation assay was assessed by flow cytometry. Findings: PBMC from infected patients showed lower frequency of CD4+ but no change in CD8+ T cells when compared with the healthy donor group. The ratio CD4+/CD8+ was 1.3, 0.6 and 0.5 in healthy donors, infected and non‐infected individuals, respectively. The HLA‐DR+ expression on CD8+ was higher in PBMC from infected and non‐infected individuals than from healthy donors, but similar in both total lymphocytes and CD4+ populations. No intergroup proliferation response differences were observed in CD4+ and CD8+ PBMC unstimulated and stimulated with SEA and SWAP. The SEA but not SWAP‐stimulated cells showed a decrease in the expression of phosphorylated extracellular signal‐regulated kinase (ERK1/2). Conclusions: XTO and NI individuals living in the same area presented a smaller per cent of CD4+ and a higher per cent of CD8+ cells. The activation by either CD8high+HLA‐DR+ or CD8high+HLA‐DR+/CD8+ was enhanced and decreased in XTO and NI by CD8+ CD28+ and CD8+ CD28+/CD8+ when compared with healthy donor. ERK phosphorylation was attenuated in XTO and NI individuals when stimulated with SEA but not SWAP.

Cytokine profile, proliferation and phosphorylation of ERK1/2 and Akt in circulating mononuclear cells from individuals during the chronic intestinal phase of Schistosomiasis mansoni infection

“…In a previous study [24], an increase in HLA-DR expression was observed on CD8 + T cells without in vitro stimulation. However, when we evaluated the expression of activation markers in the NI and XTO groups after SEA and SWAP stimulation, (Figure 1) there was no increase of any marker compared to the BD group.…”

“…In patients during the chronic intestinal phase of schistosomiasis, cell proliferation is reduced in SEA-stimulated PBMCs compared to uninfected individuals [3]. Our previous findings [24] showed no difference between T cell proliferation in the XTO, NI and BD groups after both SEA and SWAP stimulation. However, the proliferation profile in this study is consistent with the findings of most other studies [3,4,27,28] that show lower CD4 + and CD8 + T cell proliferation in the XTO group than the BD group after SEA stimulation (Figure 2C and 2D).…”

Cytokine Pattern of T Lymphocytes in AcuteSchistosomiasis mansoniPatients following Treated Praziquantel Therapy

“…Studies developed by Pancré et al [49] in murine model demonstrated that SEA was able to stimulate IFN- γ or IL-2 producing CD8 + T cells, suggesting a type 1 response induced by SEA. In humans, Oliveira-Prado et al [50] showed a smaller percent of CD4 + and a higher percent of CD8 + cells in peripheral blood from patients with chronic schistosomiasis. Moreover, our group has previously described the putative role of CD8 + T subsets in controlling morbidity during human schistosomiasis, which was evidenced by the increased levels of activated HLA-DR + CD8 + T lymphocytes in patients presenting intestinal clinical form (INT) of the disease and low levels of CD28 + CD8 + cells in hepatosplenic patients [51–53].…”

High pathogen burden in childhood promotes the development of unconventional innate-like CD8+ T cells

“…Regardless of this understandable criticism, our longitudinal childhood cohort study was able to demonstrate remarkable differences in CD8 + T cell subsets associated with prolonged pathogen exposure, notably to malaria and Schistosomiasis. The role of Schistosomiasis in shaping human T cell lineage and fate decisions is speculative at this stage, but Schistosomiasis has been shown to activate CD8 + T cells (50). Additionally, the distinctive plasma composition observed in the Kisumu compared with the Nandi children displays another layer of complexity generally overlooked in human immunology studies.…”