| First Author | Eo SK | Year | 2001 |
| Journal | J Immunol | Volume | 167 |
| Issue | 7 | Pages | 3592-9 |
| PubMed ID | 11564771 | Mgi Jnum | J:119139 |
| Mgi Id | MGI:3701368 | Doi | 10.4049/jimmunol.167.7.3592 |
| Citation | Eo SK, et al. (2001) Plasmid DNA encoding CCR7 ligands compensate for dysfunctional CD8+ T cell responses by effects on dendritic cells. J Immunol 167(7):3592-9 |
| abstractText | Lymphotoxin alpha-deficient (LTalpha-/-) mice, which lack lymph nodes and possess a disorganized spleen, develop dysfunctional CD8+ T cells upon HSV infection and readily succumb to herpes encephalitis. Such mice do develop apparently normal peptide-specific CD8+ T cell responses, as measured by MHC class I tetramer staining, but the majority of cells fail to become cytotoxic or express peptide-induced IFN-gamma production. In the present study, we demonstrate that functional defects of CD8+ T cells in LTalpha-/- mice can be largely rectified by the administration of plasmid DNA encoding CCR7 ligands before HSV infection. Treated mutant mice developed increased peptide-specific cytotoxic responses, enhanced numbers of CD8+ T cells capable of producing IFN-gamma, as well as improved resistance to HSV challenge. The corrective effect of chemokine treatment appeared to result from improved dendritic cell-mediated Ag presentation. Thus, a major consequence of the treatment was an increase in splenic dendritic cell number in CCR7 ligand-treated LTalpha-/- mice with such splenocyte populations showing improved APC activity in vitro. Our results document that functional defects of CD8+ T cells can be corrected, and indicate the value of plasmid vector encoding appropriate chemokines to achieve such immunotherapy. |
