Despite the developments in neonatology and
improvements in technology to manage preterm neonates which increased the
survival of preterm neonates, however, the relative risk of neonatal death is
much greater for preterm infants than for full-term (1). Neonatal sepsis and
bronchopulmonary dysplasia are the most frequent causes of death in premature
newborns (2). The
immune response in preterm infants is affected by prenatal factors including in
utero inflammation and maternal characteristics (3,4). Regulatory T
cells (Tregs) are a population of CD4+ T cells that play an important role
in peripheral tolerance and control of immune responses to pathogens. They
making up 5% to 10% of the normal CD4+ T-cell population and characterized by
the expression of the CD25 surface marker and the transcription factor forkhead
box protein 3 (Foxp3) (5). Tregs play a vital role in
maternal–fetal tolerance, and their levels are increased during pregnancy
participate in abrogating immune
responses and prevent exacerbated and harmful immune activation. However, Tregs may inhibit the
antimicrobial immune responses
lead to ineffective clearance of pathogens resulting in persistent infection 8.
Tregs were divided based on their expression of CD45RA.
CD4+FoxP3+ CD45RA+ cells were described as naive or resting Tregs, while CD4+
FoxP3+CD45RA- cells were regarded as fully functional effector Tregs. CD4+
FoxP3+ CD45RA- cells are cytokine-secreting, non-suppressive T cells (9).The
naïve subset are de novo generated cells which recently released from the
thymus and have not yet experienced antigen exposure 10.
Tregs express several molecules associated with their suppressive function.
.About 40 % of the Tregs show surface HLA-DR expression.. HLA-DR+ Tregs express
induced a more intense and a more rapid T cell suppression than the Tregs that
lack HLA-DR expression 11.
Other way for Tregs to suppress
effector T cells directly seems to be by transferring cyclic adenosine
monophosphate (cAMP) into the responder cells 12. cAMP is a potent inhibitor
of proliferation, differentiation and IL-2 synthesis in T cells 13. CD39 is
an ectoenzyme that degrades ATP to AMP and may be involved in suppression
mediated by Tregs. CD39 is expressed by all Treg in mice and to a lesser and
variable extent in humans 14.
There are Previous studies of the expression of
activation and memory markers (CD45RO, CD69, HLA-DR, CD25) on total cord blood
CD4+ cells in neonates
15,16 however, there is
no studies about the expression of theses
markers on cord blood Tregs
is little information about immunity in neonates and the capacity of their
immune systems against infections especially in preterm infants. The immune
response of preterm infants is suspected to be immature; however, the data on
differences in immune capacity between preterm and full-term infants are scant.
The aim of this study was to study Tregs and their expression of
CD45RA, HLA-DR, and CD39 in newborn infants.