Abstract
BackgroundCD8+ T cells have been shown to play a crucial role in Trypanosoma cruzi infection. Memory CD8+ T cells can be categorised based on their distinct differentiation stages and functional activities as follows: stem cell memory (TSCM), central memory (TCM), transitional memory (TTM), effector memory (TEM) and terminal effector (TTE) cells. Currently, the immune mechanisms that control T. cruzi in the chronic phase of the infection are unknown.Methodology/Principal FindingsTo characterise the CD8+ T cell subsets that could be participating in the control of T. cruzi infection, in this study, we compared total and T. cruzi-specific circulating CD8+ T cells with distinctive phenotypic and functional features in chronic chagasic patients (CCPs) with different degrees of cardiac dysfunction. We observed a decreased frequency of total TSCM along with an increased frequency of TTE in CCPs with severe disease. Antigen-specific TSCM cells were not detectable in CCPs with severe forms of the disease. A functional profile of CD8+ T cell subsets among CCPs revealed a high frequency of monofunctional CD8+ T cells in the most severe patients with IFN-γ+- or TNF-α+-producing cells.Conclusions/SignificanceThese findings suggest that CD8+ TSCM cells may be associated with the immune response to T. cruzi and outcome of Chagas disease, given that these cells may be involved in repopulating the T cell pool that controls infection.
Highlights
The memory CD8+ T cell compartment comprises cells that represent distinct differentiation stages and different functional activities
We have characterised the memory CD8+ T cell subsets in chronic chagasic patients, including a newly described population of cells called memory stem cells. This T cell subset seems important for replenishing the other T cell populations. The findings in this manuscript show that chronic chagasic patients with severe disease have the following: a) a low frequency of memory stem cells, b) no antigen-specific memory stem cells, and c) CD8+ T cells with less effector function compared with asymptomatic patients
These results indicate that the lack of T cell population renewal and the decrease in cells with multiple effector functions may be associated with the clinical outcome of chronic Chagas disease
Summary
The memory CD8+ T cell compartment comprises cells that represent distinct differentiation stages and different functional activities. This cellular compartment has been divided into stem cell memory (TSCM), central memory (TCM), transitional memory (TTM), effector memory (TEM) and terminal effector (TTE) cells [1]. As a potential reservoir to maintain and to replenish the memory T cell pool, TSCM cells represent a potential tool for cellular immune therapies in chronic infectious diseases. Memory CD8+ T cells can be categorised based on their distinct differentiation stages and functional activities as follows: stem cell memory (TSCM), central memory (TCM), transitional memory (TTM), effector memory (TEM) and terminal effector (TTE) cells. The immune mechanisms that control T. cruzi in the chronic phase of the infection are unknown
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