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Development of the dendritic cell system during mouse ontogeny.
Aleksandar Dakic1, Qi-xiang Shao, Angela D'Amico
1The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Journal of Immunology (Baltimore, Md. : 1950)
|January 7, 2004
Summary
The neonatal immune system, particularly dendritic cells (DCs), is not fully developed at birth. Adaptive immunity requires 5 weeks for full development in mice, with innate immunity dominating early responses.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- Immune system efficacy correlates with immune cell maturation.
- Dendritic cells (DCs) are crucial for immune responses.
- Understanding DC development is key to understanding immune system maturation.
Purpose of the Study:
- Investigate the development and function of conventional DCs and plasmacytoid pre-DCs (p-preDCs) during mouse development.
- Characterize DC populations in spleen, thymus, and lymph nodes.
- Assess the functional capacity of neonatal versus adult DCs.
Main Methods:
- Flow cytometry analysis of splenic, thymic, and lymph node cells.
- Detection of CD11c+ DCs and CD45RA+ p-preDCs at various developmental stages (embryonic day 17, 1 week, 5 weeks).
- Assessment of cytokine production (IFN-alpha, IL-12p70, IFN-gamma) and antigen presentation capacity.
Main Results:
- DCs and p-preDCs appear in the thymus by embryonic day 17 and reach adult ratios by 1 week.
- Spleens contain low numbers of DCs and p-preDCs at birth, with full complement by 5 weeks.
- Neonatal splenic DC composition differs significantly from adults, with altered CD4/CD8alpha ratios.
- Neonatal p-preDCs produce IFN-alpha similarly to adults, but conventional DCs show reduced IL-12p70 and IFN-gamma production and antigen presentation.
Conclusions:
- The neonatal dendritic cell system is immature, with innate immunity being the primary response.
- Full development of the DC system necessary for adaptive immunity in mice is achieved by 5 weeks of age.
- Neonatal conventional DCs exhibit functional deficits compared to adult DCs.