Lower peripheral blood CD14+ monocyte frequency and higher CD34+ progenitor cell frequency are associated with HBV vaccine induced response in HIV infected individuals.

We evaluated immunologic predictors of response to HBV vaccine administered in the presence or absence of GM-CSF in HIV infected individuals. We measured peripheral blood hematopoietic progenitor, monocyte and myeloid-derived suppressor cell (MDSC) frequencies, and expression of GMCSF receptor on monocytes and MDSCs, at baseline and 4weeks after immunization in relation to antibody response. We observed higher baseline progenitor and lower monocyte frequencies among week 16 antibody responders. Week 4 decline in MDSC frequency was associated with week 16 antibody response, while administration of GM-CSF was associated with preservation of these cells. No significant differences in GM-CSF receptor expression were observed in the presence vs. absence of GM-CSF. These findings are consistent with a positive role of progenitor cells and a potential negative role of monocytes in vaccine response. Additionally, GM-CSF augmented the preservation of peripheral blood MDSC, which may contribute to the lack of improved vaccine responses.

Granulocyte transfusions in septic adult and newborn rats: distribution of granulocytes and effect on peripheral blood and bone marrow.

Granulocyte transfusions are increasingly being used as therapy for newborns with sepsis and neutropenia. We injected either group B Streptococcus or phosphate-buffered saline solution intraperitoneally into adult and newborn rats. Human granulocytes, labeled with chromium 51, were transfused seven hours later. When the newborn rats were killed 13 to 19 hours after injection, they had 10(2) to 10(6) cfu/gm Streptococcus organisms in both lung and brain. Only one third of the adult rats had 10(2) to 10(4) cfu/gm Streptococcus organisms in either lung or brain. A greater proportion of the transfused granulocytes was present in lung and brain tissue of newborn rats, compared with adult rats (p less than 0.05), irrespective of infection. Granulocyte transfusion did not change the peripheral blood leukocyte count in adult rats but increased the count in newborn rats (p less than 0.05). The immature myeloid pool in the bone marrow of adult rats increased significantly with either infection or transfusion (p less than 0.01). The immature pool in newborn rats increased significantly only with infection (p greater than 0.001), although the combination of infection and transfusion also had a significant effect on the pool (p less than 0.01). Infection and both infection and transfusion, but not transfusion alone, significantly affected the mature myeloid bone marrow pool in adult and newborn rats (p less than 0.001). The depletion of the mature myeloid elements of the bone marrow in response to infection was dramatic in neonatal rats, compared with that in adult rats. Both transfused granulocytes and hematogenously spread streptococci lodge in the brains and lungs of neonatal rats more effectively than in those of adult rats.

Impaired surface membrane expression of C3bi but not C3b receptors on neonatal neutrophils.

Because increased complement receptor expression is necessary for optimal function of adult neutrophils, we tested the hypothesis that the increased susceptibility of neonates to infection might be due to an impaired ability of neonatal neutrophils to increase expression of complement receptors in response to chemotactic stimuli. We used monoclonal antibodies and flow cytometry to compare surface expression of the receptors for the complement components C3b (CR1) and C3bi (CR3) on adult and neonatal cord blood neutrophils (PMNs). We also compared receptor expression on PMNs from infants delivered by cesarean section without labor versus infants delivered vaginally. Expression of both CR1 and CR3 was minimal on resting adult and neonatal PMNs maintained at 0 degrees C. There was a modest increase in expression of both receptors when PMNs were warmed to 37 degrees C. This increase was similar on adult and neonatal cells, both unfractionated in whole blood and after isolation with Percoll density centrifugation, with one exception. Expression of CR1 was greater on isolated PMNs from vaginally delivered infants versus adults when the cells were warmed to 37 degrees C. This difference was not observed with cells from infants delivered by cesarean section without labor, suggesting this modest increase in receptor expression may be due to factors associated with labor. When isolated cells were stimulated with either N-formyl-methionyl-leucyl-phenylalanine or zymosan-activated serum, expression of CR1 increased to the same extent in both neonatal and adult PMNs. In contrast, maximal CR3 expression on cord PMNs stimulated with N-formyl-methionyl-leucyl-phenylalanine or zymosan-activated serum was only 75% of the adult values.(ABSTRACT TRUNCATED AT 250 WORDS)