First Author | Sacks JA | Year | 2008 |
Journal | J Immunol | Volume | 180 |
Issue | 7 | Pages | 4570-6 |
PubMed ID | 18354179 | Mgi Jnum | J:132990 |
Mgi Id | MGI:3777499 | Doi | 10.4049/jimmunol.180.7.4570 |
Citation | Sacks JA, et al. (2008) TRAIL Deficiency Does Not Rescue Impaired CD8+ T Cell Memory Generated in the Absence of CD4+ T Cell Help. J Immunol 180(7):4570-6 |
abstractText | Ag-specific CD8(+) T cells immunized in the absence of CD4(+) T cell help, so-called 'unhelped' CD8(+) T cells, are defective in function and survival. We investigated the role of the proapoptotic molecule TRAIL in this defect. We first demonstrate that TRAIL does not contribute to the CD8(+) T cell response to Listeria monocytogenes strain expressing OVA (LmOVA) in the presence of CD4(+) T cells. Secondly, we generated mice doubly deficient in CD4(+) T cells and TRAIL and analyzed their CD8(+) T cell response to LmOVA. Memory CD8(+) T cells in double-deficient mice waned over time and were not protective against rechallenge, similar to their TRAIL-sufficient unhelped counterparts. To avoid the effects of CD4(+) T cell deficiency during memory maintenance, and to address whether TRAIL plays a role in the early programming of the CD8(+) T cell response, we performed experiments using heterologous prime and early boost immunizations. We did not observe activation-induced cell death of unhelped CD8(+) T cells when mice were infected with followed vaccinia virus expressing OVA 9 days later by LmOVA infection. Furthermore, primary immunization of CD4(+) T cell-deficient mice with cell-associated Ag followed by LmOVA infection did not reveal a role for TRAIL-mediated activation-induced cell death. Overall, our results suggest that CD4(+) T cell help for the CD8(+) T cell response is not contingent on the silencing of TRAIL expression and prevention of TRAIL-mediated apoptosis. |