Our understanding of adaptive immunity in both mouse and human neonates has advanced significantly over the past decade.
Previously thought to be immunodeficient or immunodeviant, it is now clear that neonatal cells from all arms of the adaptive immune system can achieve mature function under the right conditions.
An ever-increasing body of evidence indicates that the neonatal period of life is a unique developmental window in which responses are highly plastic.
Although mature function can be elicited under some circumstances, neonatal immune responses are often dampened or non-protective.
Factors contributing to these non-mature responses might include the reduced number of immune cells in neonates compared with adults, the presence of immune cells derived from fetal haematopoietic precursors in neonates but not adults, apoptosis of selective subsets of T helper cells and the unique neonatal environment, which promotes homeostatic proliferation of both CD4+ and CD8+ T cells.
The malleability of neonatal immune responses predicts that mature responses to vaccines should be achievable. However, further research in mice and humans is crucial to determine that agents used to boost immunity in neonates have neither short- nor long-term pathological effects.
The past decade has brought great strides in our understanding of adaptive immunity in neonatal mice. Although poor immune responses are commonly observed, it is now clear that mature function can be achieved by all arms of the adaptive immune system. An ever-increasing body of evidence indicates that the neonatal period of life is a unique developmental stage in which responses are highly plastic and dependent on the conditions of antigen exposure. This review focuses on our new understanding in mice and, where it is clear that related phenomena occur, in humans.
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- TH1/TH2-CELL POPULATIONS
At least two distinct subsets of activated CD4+ T cells have been described. T helper 1 (TH1) cells produce interferon-γ, lymphotoxin and tumour-necrosis factor, and support cell-mediated immunity. TH2 cells produce interleukin-4 (IL-4), IL-5 and IL-13, support humoral immunity and downregulate TH1-cell responses.
- NEONATAL MICE
Newborn mice are defined experimentally as those ranging in age from 1 to 10 days. Although there are major changes in lymphoid-organ development during the first week of life, at least some adaptive immune responses are similar in 1-day-old and 7-day-old mice. Nonetheless, mice are immunologically less mature at birth than humans and it has been proposed that 7-day-old mice are most comparable to human newborns.
- CPG MOTIFS
DNA oligodeoxynucleotide sequences that include a cytosine–guanosine sequence and certain flanking nucleotides, which have been found to induce innate immune responses through interaction with Toll-like receptor 9.
- SEVERE COMBINED IMMUNODEFICIENT
(SCID). Mice of this phenotype lack functional T and B cells, owing to a spontaneous mutation in the Prkdc gene (protein kinase, DNA activated, catalytic polypeptide) located on chromosome 16. These mice can be reconstituted with T-cell subsets and used to study T-cell functions in vivo.
- REGULATORY T CELLS
(TReg cells). Naturally occurring TReg cells contribute to the maintenance of immunological self-tolerance and modulate the reactivity of other T cells. They constitute a network of heterogeneous CD4+ T-cell subsets, CD8+ T cells and other minor T-cell populations.
- T-CELL-DEPENDENT ANTIBODY RESPONSES
Antibody responses to protein antigens that require recognition of the antigen by T helper cells and cooperation between antigen-specific B and T cells.
- T-CELL-INDEPENDENT ANTIBODY RESPONSES
Antibody responses to polymeric antigens, such as polysaccharides and lipids, that do not require T-cell help.
- B1-CELL LINEAGE
IgMhiIgDlowMac1+B220lowCD23− cells that are dominant in the peritoneal and pleural cavities. Their precursors develop in the fetal liver and omentum, and in adult mice, the size of the B1-cell population is kept constant owing to the ability of these cells to self-renew. B1 cells recognize self components, as well as common bacterial antigens, and secrete antibodies that tend to have low affinity and broad specificity.
- PLASMACYTOID DCs
A subset of dendritic cells (DCs) that were first described in humans and termed plasmacytoid because of their microscopic appearance, which is similar to plasmablasts. In humans, these DCs can be derived from lineage-negative stem cells in peripheral blood and are the main producers of type I interferon (IFN) in response to virus infections. Recent studies have identified a subset of type I IFN-producing DCs in mice, which are characterized by expression of B220 and Ly6C/G.
Refers to the heritable, but potentially reversible, states of gene activity that are imposed by the structure of chromatin or covalent modifications of DNA and histones.
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Adkins, B., Leclerc, C. & Marshall-Clarke, S. Neonatal adaptive immunity comes of age. Nat Rev Immunol 4, 553–564 (2004). https://doi.org/10.1038/nri1394
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