A joint Institut Pasteur-Inserm team has deciphered key mechanisms in the development of newborn immune systems. This study has made it possible to understand why infants are susceptible to early infections that cause high mortality rates, particularly in developing countries. Understanding these mechanisms offers possibilities for new types of treatment and vaccines adapted to protect newborns.
Press release
Paris, april 19, 2005
Neonates exhibit less efficient immune responses to pathogens than adults because a specific regulatory mechanism prevents the induction of an appropriate response to fight many types of infections. This was demonstrated in mice by Richard Lo-Man, Claude Leclerc and their colleagues (Biology of Immune System Regulations Unit, Inserm Team 352) at Institut Pasteur in Paris.
A key link in the immune system response, CD4+ T-lymphocytes, can be divided into two subgroups according to their properties: Th1 lymphocytes specifically attack intracellular pathogens and viral infections, while Th2 lymphocytes primarily attack parasites and are also involved in allergies. Although it was well-known that newborn immune responses are essentially of the Th2 type, which explains why babies are so susceptible to many infections, the mechanisms that made this orientation different from that of adults had been remained unclear until now.
These researchers have shown that the newborn’s T-lymphocytes are perfectly capable of differentiating into Th1 lymphocytes and can therefore learn to recognize and fight pathogens. It is the cell environment, and more specifically, the "CD5+" B-lymphocytes, in conjunction with the dendritic cells, which are essential for stimulating immune responses, that inhibits the Th1 differentiation and favors the Th2 category. This study has established that the dendritic cells in newborn mice, when placed in a favorable environment, engage the T-cells toward the Th1 category. Researchers have also successfully induced the activation of dendritic cells, in vitro, enabling Th1 differentiation from neonatal T-cells. This was achieved by stimulating them using small synthetic molecules. However, the researchers conducting this study have proven that this stimulation is inhibited in newborns by the production of a high level of interleukin-10, a natural anti-inflammatory molecule produced by the CD5+ B-lymphocytes.
Understanding these early regulatory mechanisms of the immune system offers possibilities for the development of treatments that can fight infections in infants and prevent early allergy problems. It also offers precious information that can be used to develop specially-adapted vaccines to protect newborns.
Sources
"Upon TLR9 signaling, CD5+ B cells control the IL-12-dependent Th1-priming capacity of neonatal DCs" : Immunity, April 17, 2005.
Cheng-Ming Sun, Edith Deriaud, Claude Leclerc and Richard Lo-Man
Biology of Immune System Regulations Unit & Inserm Team 352
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