CD169⁺ macrophages are sufficient for priming of CTLs with specificities left out by cross-priming dendritic cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 17; pp. 5461 - 5466
• Main Authors: Bernhard, Caroline A., Ried, Christine, Kochanek, Stefan, Brocker, Thomas
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 28.04.2015; National Acad Sciences
• Subjects: Animals; Antigen Presentation - physiology; Antigens; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; Bias; Biological Sciences; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cells; Cross Reactions - immunology; Cytotoxicity; Dendritic Cells - cytology; Dendritic Cells - immunology; Epitopes, T-Lymphocyte - immunology; Lectins, C-Type - immunology; Leukocytes; Mice; Peptides; Rodents; CD8 T cell; CD169+ macrophage; cross-presentation; dendritic cell; adenovirus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1423356112

Dendritic cells (DCs) are considered the most potent antigen-presenting cells (APCs), which directly prime or cross-prime MHC I-restricted cytotoxic T cells (CTLs). However, recent evidence suggests the existence of other, as-yet unidentified APCs also able to prime T cells. To identify those APCs, we used adenoviral (rAd) vectors, which do not infect DCs but selectively accumulate in CD169 ⁺ macrophages (MPs). In mice that lack DCs, infection of CD169 ⁺ MPs was sufficient to prime CTLs specific for all epitopes tested. In contrast, CTL responses relying exclusively on cross-presenting DCs were biased to selected strong MHC I-binding peptides only. When both DCs and MPs were absent, no CTL responses could be elicited. Therefore, CD169 ⁺ MPs can be considered APCs that significantly contribute to CTL responses. Significance Although we know much about the molecular mechanisms of cross-presentation, its actual contribution to cytotoxic T cell (CTL) immunity under physiological conditions in vivo is still unclear. Cross-presentation is based on the idea that dendritic cells (DCs) are the only professional antigen-presenting cells able to prime naïve T cells. If DCs are not directly infected, they must take up antigen and present it indirectly. However, recent evidence suggests that other cells also may be involved in T cell priming, which probably makes cross-presentation less central. This study shows that cross-priming DCs generate highly restricted CTL repertoires, biased to strong MHC I binding epitopes only. Furthermore, the presence of antigen in CD169 ⁺ macrophages is sufficient for generation of CTLs with broader repertoires.