Expression and regulation of B7 family molecules on macrophages (MPhi) in preterm and term neonatal cord blood and peripheral blood of adults.
BACKGROUND
Macrophage (MPhi) receptors of the B7 family (CD80, CD86) play a crucial role in T cell activation: the lack of costimulation leads to anergy or apoptosis of reactive T cells. MPhi may differentiate into different subsets, the balance of which defines MPhi-dependent T cell reactions. The aim of this study was to examine neonatal and adult T cell response with respect to the costimulatory MPhi-potential in order to identify molecular predictors for the neonatal immune defense.


METHODS
MPhi from peripheral blood (PBMPhi) or cord blood (CBMPhi) were stimulated with interferon-gamma (IFN-gamma), cyclic adenosine monophosphate (cAMP), CD40 ligand (CD40L), or alphaCD3.


RESULTS
As compared to PBMPhi, CBMPhi showed a significantly decreased upregulation of CD80 and/or CD86 after stimulation with IFN-gamma, cAMP, CD40L, and alphaCD3. Accordingly, the proliferative T cell response was impaired in the presence of CBMPhi. The fraction of T cells that underwent cell death was higher, and blast formation was significantly lower than that observed in the presence of PBMPhi.


CONCLUSIONS
CBMPhi, as compared to PBMPhi, delivered fewer costimulatory but more cytotoxic signals to T cells. These observations suggest that MPhi are one factor explaining the suboptimal immune defense of neonates and their increased susceptibility to infection. Using the costimulatory MPhi-potential as a predictor for immune responses requires a separate reference value system in neonatology.
Orlikowsky
Thorsten W
TW
University Childrens Hospital, Tübingen, Germany. thorsten.orlikowsky@med.uni-tuebingen.de
Spring
Bärbel
B
Dannecker
Günther E
GE
Niethammer
Dietrich
D
Poets
Christian F
CF
Hoffmann
Michael K
MK
D000328:Adult; D000367:Age Factors; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000494:pharmacology; D023201:CD40 Ligand / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D017252:CD3 Complex; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D007371:Interferon-gamma; D000242:Cyclic AMP