Abstract
Chronic lymphatic filarial (LF) infection is associated with suppression of parasite-specific T cell responses that persist even following elimination of infection. While several mechanisms have been implicated in mediating this T cell specific downregulation, a role for alterations in the homeostasis of T effector and memory cell populations has not been explored. Using multiparameter flow cytometry, we investigated the role of persistent filarial infection on the maintenance of T cell memory in patients from the filarial-endemic Cook Islands. Compared to filarial-uninfected endemic normals (EN), microfilaria (mf) positive infected patients (Inf) had a reduced CD4 central memory (TCM) compartment. In addition, Inf patients tended to have more effector memory cells (TEM) and fewer effector cells (TEFF) than did ENs giving significantly smaller TEFF ∶ TEM ratios. These contracted TCM and TEFF populations were still evident in patients previously mf+ who had cleared their infection (CLInf). Moreover, the density of IL-7Rα, necessary for T memory cell maintenance (but decreased in T effector cells), was significantly higher on memory cells of Inf and CLInf patients, although there was no evidence for decreased IL-7 or increased soluble IL7-Rα, both possible mechanisms for signaling defects in memory cells. However, effector cells that were present in Inf and CLInf patients had lower percentages of HLA-DR suggesting impaired function. These changes in T cell populations appear to reflect chronicity of infection, as filarial-infected children, despite the presence of active infection, did not show alterations in the frequencies of these T cell phenotypes. These data indicate that filarial-infected patients have contracted TCM compartments and a defect in effector cell development, defects that persist even following clearance of infection. The fact that these global changes in memory and effector cell compartments do not yet occur in infected children makes early treatment of LF even more crucial.
Highlights
Lymphatic filariasis (LF) is a chronic helminth infection that is associated with a profound parasite-specific T cell hyporesponsiveness in individuals with patent infection
endemic normals (EN) vs infected patients (Inf) vs cleared their infection (CLInf) Subjects Because the major objectives of this study were to assess the consequences of a chronic helminth infection on effector and memory cell populations and to understand whether the clearance of lingering Ag alters these populations, a comparison was made between endemic normal (EN) individuals to those who had clear evidence of long-standing, active filarial infection at both time periods (Inf)
There were no significant differences in the percentage of naıve T cells among the groups, there was an increase in the relative size of the naıve compartment in the EN group compared to either the Inf or CLInf groups, for CD4+ cells (Table 2)
Summary
Lymphatic filariasis (LF) is a chronic helminth infection that is associated with a profound parasite-specific T cell hyporesponsiveness in individuals with patent infection. Mechanisms underlying this diminished antigen (Ag)-specific T cell response have included: 1) increased production of IL-10 and/or the expansion of IL-10 producing CD4+ T cells [1,2,3,4]; 2) in utero exposure to the parasite [5,6] 3) altered Ag presenting cell function [7,8]; and 4) apoptosis of Ag-activated cells [9]. Of even more broad-reaching importance is the impaired response to parenterally- [20,21] and orally- [22] administered vaccines seen in those with intestinal or tissue invasive helminth infections
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