T follicular helper cells in patients with acute schistosomiasis
Zhang et al. Parasites & Vectors
T follicular helper cells in patients with acute schistosomiasis
i Yin 0 1 2 5
nping C
0 National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention , Shanghai 200025 , China
1 National Center for International Research on Tropical Diseases , Shanghai 200025 , China
2 Key Laboratory of Parasite and Vector Biology, MOH , Shanghai 200025 , China
3 Department of Pathogenic Biology and Immunity, Xuzhou Medical University , Xuzhou 221004, Jiangsu , China
4 Department of Pathogenic Biology, Binzhou Medical University , Yantai 264003, Shandong , China
5 WHO Collaborating Center for Tropical Diseases , Shanghai 200025 , China
Background: The role of T follicular helper (Tfh) cells in schistosome infection is not fully defined. In a previous study, a higher frequency of circulating PD-1+CXCR5+CD4+ Tfh cells was observed in patients with chronic schistosomiasis relative to healthy controls (HCs) and it correlated positively with the level of soluble egg antigen (SEA) specific antibodies in serum. However, the function of Tfh cells in patients with acute schistosomiasis remains elusive; this was investigated in the present study. Methods: The frequency of circulating Tfh cells and the expression of inducible T cell co-stimulator (ICOS), programmed cell death 1 (PD-1) and B cell subsets were analyzed in 12 patients with acute schistosomiasis and 10 HCs by flow cytometry. The expression of Bcl6, c-Maf and IL-21 mRNA were detected by quantitative real-time reverse transcriptase PCR (qRT-PCR). The concentration of serum IL-21 and IgG specific to Schistosoma japonicum antigen were then determined by enzyme linked immunosorbent assay (ELISA). Correlations between PD-1+CXCR5+CD4+ Tfh cells, memory B cells and IgG specific to S. japonicum were analyzed by Spearman's rank correlation. Results: The frequency of PD-1+CXCR5+CD4+ Tfh and memory B cells was increased in acute schistosomiasis patients relative to HCs. Moreover, the levels of IL-21 in serum and the expression of IL-21 mRNA were higher in acute schistosomiasis patients. However, there was no significant correlation between PD-1+CXCR5+CD4+ Tfh cells, memory B cells and IgG specific to S. japonicum antigen in patients with acute schistosomiasis. Conclusions: PD-1+CXCR5+CD4+ Tfh cells in peripheral blood are involved in the immune response of patients with acute schistosomiasis. Understanding the immunological mechanism is helpful for the development of vaccination strategies to control schistosomiasis.
T follicular helper cells; PD-1; IL-21; Acute schistosomiasis
Background
Schistosomiasis is a serious public health problem in
many developing countries. More than 200 million
people are infected and 700 million people are at risk of
becoming infected [
1, 2
]. There is no effective
antischistosome vaccine because of insufficient knowledge
of immunological responses to schistosomiasis. Humoral
immunity is crucial for successful vaccines. Recent
studies reveal Tfh cells are a separate subset of CD4+ T cells
that are mainly responsible for promoting B cells to
undergo proliferation, isotype switching and antibody
response [
3–5
]. Recently, a study showed that Tfh cells
were recruited to the liver and upregulated hepatic
granuloma formation and liver injury in S.
japonicum-infected mice [6]. Our previous study showed that Tfh
cells might play an important role in the production of
specific antibodies in chronic schistosomiasis patients
[
7
], but their function in acute schistosomiasis patients
is unknown.
Although Tfh cells in the germinal center (GC) zones
are easily detected, it is difficult to obtain lymph nodes
or spleen from schistosomiasis patients. Circulating Tfh
cells were reported to share some features of GC Tfh
cells [
8
], thus analysis of circulating Tfh cells may be an
effective alternative approach to studying GC Tfh cells in
humans. In this paper, we determined the characteristics
of circulating Tfh cells in acute schistosomiasis patients.
PD-1+CXCR5+CD4+ Tfh cells were significantly increased
and were involved in the immune response. These data
contribute to understanding the role of Tfh cells in acute
schistosomiasis and will support vaccine development.
Methods
Ethical statement
Ethical approval for this study was obtained from the
Ethics Committee of the National Institute of Parasitic
Diseases, Chinese Center for Disease Control and
Prevention (reference no. 2012–12). This study was
conducted according to the guidelines provided in the
Declaration of Helsinki and all procedures were
approved by the Ethics Review Committee of the National
Institute of Parasitic Disease, Chinese Center for Disease
Control and Prevention. The objectives and procedures
of the study were verbally explained to each participant
and written informed consent was obtained.
Patients and healthy controls
The study was carried out on a total of 22 subjects from
Dongting Lake Basin, Hunan Province, (...truncated)