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Rapid high efficiency sensitization of CD8+ T cells to tumor antigens by dendritic cells leads to enhanced functional avidity and direct tumor recognition through an IL-12-dependent mechanism.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Xu, Shuwen Koski, Gary K. Faries, Mark B. Bedrosian, Isabelle Mick, Rosemarie Maeurer, Markus Cheever, Martin A. Cohen, Peter A. Czerniecki, Brian |
| Copyright Year | 2003 |
| Abstract | Myeloid-origin dendritic cells (DCs) can develop into IL-12-secreting DC1 or non-IL-12-secreting DC2 depending on signals received during maturation. Through rapid culture techniques that prepared either mature, CD83+ DC1 or DC2 from CD14+ monocytes in only 2 days followed by a single 6-7 day DC-T cell coculture, we sensitized normal donor CD8+ T cells to tumor Ags (HER-2/neu, MART-1, and gp100) such that peptide Ag-specific lymphocytes constituted up to 16% of the total CD8+ population. Both DC1 and DC2 could sensitize CD8+ T cells that recognized peptide-pulsed target cells. However, with DC2, a general decoupling was observed between recognition of peptide-pulsed T2 target cells and recognition of Ag-expressing tumor cells, with peptide-sensitized T cells responding to tumor only about 15% of the time. In contrast, direct recognition of tumor by T cells was dramatically increased (to 85%) when DC1 were used for sensitization. Enhanced tumor recognition was accompanied by 10- to 100-fold increases in peptide sensitivity and elevated expression of CD8beta, characteristic of high functional avidity T cells. Both of these properties were IL-12-dependent. These results demonstrate the utility of rapid DC culture methods for high efficiency in vitro T cell sensitization that achieves robust priming and expansion of Ag-specific populations in 6 days. They also demonstrate a novel function of IL-12, which is enhancement of CD8+ T cell functional avidity. A new approach to DC-based vaccines that emphasizes IL-12 secretion to enhance functional avidity and concomitant tumor recognition by CD8+ T cells is indicated. |
| File Format | PDF HTM / HTML |
| DOI | 10.4049/jimmunol.171.5.2251 |
| PubMed reference number | 12928369 |
| Journal | Medline |
| Volume Number | 171 |
| Issue Number | 5 |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/171/5/2251.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.4049/jimmunol.171.5.2251 |
| Journal | Journal of immunology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
