The role of antigen-donor cell death in CD8 T cell activation in Histoplasma capsulatum infection
Date Issued
2007
Date
2007
Author(s)
Hsieh, Shi-Hong
DOI
en-US
Abstract
Histoplasma capsulatum (Hc) is an intracellular pathogen residing in the phagosomal compartment of the macrophages. In vitro studies showed that the yeast cells induce macrophage apoptosis. We have also reported that DCs which have engulfed Hc-infected apoptotic macrophages stimulate sensitized CD8 T cells in vitro and CD8 T cells are activated in animals after Hc infection. However, how CD8 T cell are activated in vivo remains unclear. Based on results of the above studies, I hypothesized that after entering the host, Histoplasma yeast cells induce macrophage apoptosis and the fungal antigen contained within the apoptotic macrophages are cross-presented by DCs to activate CD8 T cell. Thus, Histoplasma-induced host cell apoptosis would be key to CD8 T cell activation in the infected host.
In this study, I showed that subcutaneous inoculation of live Histoplasma yeasts induced neutrophil and macrophage infiltration into the injection site and both of them underwent apoptotic death. Both CD8 and CD4 T cells in the draining lymph nodes were activated to express phenotypic activation markers as well as IFN-γ. To investigate whether macrophage apoptosis is related to T cell activation, mice were injected subcutaneously with heat-killed Histoplasma-containing apoptotic macrophages. The results showed that both CD8 and CD4 T cell were activated but the magnitude of CD8 T cell activation was greater than that of CD4 T cells. In contrast, HKHc-containing nonapoptotic macrophages only triggered a minimal T cell response. These results indicate that antigen-donor cell apoptosis is important to T cell, especially CD8 T cell, activation. Furthermore, β2m-/- apoptotic macrophages were as efficient as wild-type cells in inducing CD8 T cell activation in the immunized host. It suggests that CD8 T cell activation is the result of cross-presentation by host APCs that acquired Histoplasma antigens contained within donor apoptotic macrophages. Interestingly, inoculation of HKHc-containing apoptotic macrophages protected mice against Histoplasma infection, indicating that the activated T cells are functionally activated. The results of my work contribute to the understanding of how Histoplasma host cell apoptosis is important to CD8 T cell cross-priming after Histoplasma infection.
Subjects
抗原贈與細胞
CD8 T細胞
組織胞漿菌
交叉活化
antigen-donor cell
CD8 T cell
Histoplasma capsulatum
cross-priming
Type
other
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