IL-21 and IL-15 cytokine DNA augments HSV specific effector and memory CD8+ T cell response.
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(+) IFNgamma producing cells in the primary response. In the memory phase, numbers of CD8(+) CD44(high) as well as CD8(+) T cells producing IFN-gamma and TNF-alpha 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.
Rodrigues
Luiz
L
Faculdade de Biociências e Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS 90619-900, Brazil.
Nandakumar
Subhadra
S
Bonorino
Cristina
C
Rouse
Barry T
BT
Kumaraguru
Uday
U
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004247:DNA / Q000276:immunology* / Q000502:physiology; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D007167:Immunotherapy / Q000379:methods; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D018139:Simplexvirus / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014709:Vero Cells; D000098546:Interleukin-21
D019409:Interleukin-15; D007378:Interleukins; D004247:DNA; D000098546:Interleukin-21