Article ID Journal Published Year Pages File Type
5917909 Molecular Immunology 2009 11 Pages PDF
Abstract
The recurrence of lesions and transmission of Herpes simplex virus is dependent on the number and function of viral specific CD8+ T cells, especially the memory T cells. The generation, turnover and set point of this cell population is maintained by different factors like exposure to antigen, cytokines and co-stimulatory molecules. However, the contribution of these factors in the generation and maintenance of the memory CD8+ T cell population is still controversial, since it is not clear if homeostatic proliferation driven by cytokines can overcome T cell receptor (TCR) signaling. Since, interleukin 15 (IL-15) and interleukin 21 (IL-21) are cytokines implicated in homeostatic control of CD8+ T cell pool, we constructed and used expression plasmids coding for IL-15 (pIL-15) and IL-21 (pIL-21) to expand HSV specific CD8+ T cells in an animal model. Our results showed that the IL-21 increased the frequency of CD8+ T cells in the absence of antigen, although the magnitude of this response was dependent on TCR signaling. Both pIL-15 and pIL-21 boosted the numbers of antigen specific CD8+ IFNγ producing cells in the primary response. In the memory phase, numbers of CD8+ CD44high as well as CD8+ T cells producing IFN-γ and TNF-α were increased when pIL-15 and pIL-21 were used alone or in combination, compared to vector treatment only, and association of antigen further increased the proliferative response. Our data suggest that genetic treatment with pIL-15 and pIL-21 in the presence or absence of cognate antigen can contribute to immune-enhancement against HSV.
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