Mature human Langerhans cells derived from CD34+ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactive IL-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or monocyte-derived dendritic cells Journal Article
| Authors: | Ratzinger, G.; Baggers, J.; De Cos, M. A.; Yuan, J.; Dao, T.; Reagan, J. L.; Münz, C.; Heller, G.; Young, J. W. |
| Article Title: | Mature human Langerhans cells derived from CD34+ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactive IL-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or monocyte-derived dendritic cells |
| Abstract: | The emerging heterogeneity of dendritic cells (DCs) mirrors their increasingly recognized division of labor at myriad control points in innate and acquired cellular immunity. We separately generated blood monocyte-derived DCs (moDCs), as well as Langerhans cells (LCs) and dermal-interstitial DCs (DDC-IDCs) from CD34+ hematopoietic progenitor cells. Differential expression of CD11b, CD52, CD91, and the CD1 isoforms proved useful in distinguishing these three DC types. All mature DCs uniformly expressed comparable levels of HLA-DR, CD83, CD80, and CD86, and were potent stimulators of allogeneic T cells after exposure either to recombinant human CD40L trimer or a combination of inflammatory cytokines with PGE2. moDCs, however, required 0.5-1 log greater numbers than LCs or DDC-IDCs to stimulate comparable T cell proliferation. Only moDCs secreted the bioactive heterodimer IL-12p70, and moDCs phagocytosed significantly more dying tumor cells than did either LCs or DDC-IDCs. LCs nevertheless proved superior to moDCs and DDC-IDCs in stimulating CTL against a recall viral Ag by presenting passively loaded peptide or against tumor Ag by cross-priming autologous CD8+ T cells. LCs also secreted significantly more IL-15 than did either moDCs or DDC-IDCs, which is especially important to the generation of CTL. These findings merit further comparisons in clinical trials designed to determine the physiologic relevance of these distinctions in activity between LCs and other DCs. |
| Keywords: | unclassified drug; human cell; flow cytometry; cell proliferation; phenotype; cells, cultured; cell division; cd34 antigen; cell maturation; microscopy, confocal; dendritic cell; cd40 ligand; cell differentiation; peptide; dermis; cell lineage; cell type; stem cell; antigen presentation; lymphocyte activation; dendritic cells; lymphocyte culture test, mixed; cellular immunity; antigen specificity; immunogenicity; cd11b antigen; hla-dr antigens; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; hematopoietic cell; hematopoietic stem cells; antigens, cd; protein subunits; monocyte; monocytes; phagocytosis; antigens, cd34; t lymphocyte activation; interleukin 12; cell killing; derivatization; cd52 antigen; langerhans cell; langerhans cells; cross-priming; interleukin-12; protein p70; cd9 antigen; humans; human; priority journal; article; interleukin 12 protein p70 |
| Journal Title: | Journal of Immunology |
| Volume: | 173 |
| Issue: | 4 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2004-08-15 |
| Start Page: | 2780 |
| End Page: | 2791 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15294997 |
| DOI: | 10.4049/jimmunol.173.4.2780 |
| DOI/URL: | |
| Notes: | J. Immunol. -- Cited By (since 1996):94 -- Export Date: 16 June 2014 -- CODEN: JOIMA C2 - 15294997 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work