Plasmacytoid Dendritic Cell Counts Research Articles

Causal association of immune cells and endometritis: a Mendelian randomization study

Research exploring the link between immune cell profiles and the development of endometritis remains scant. This gap necessitates further study to decode the complex interrelations influencing this condition. In this analysis, we leveraged two-sample Mendelian randomization to examine the causal ties between the phenotypes of immune cells and the incidence of endometritis. Our evaluation hinged on data from 3757 participants hailing from Sardinia, focusing on a diverse array of 731 immune phenotypes, and cross-referenced with endometritis data sourced from the UK Biobank. To ensure rigor, we performed sensitivity analyses, utilized MR-Egger and MR-Presso to check for pleiotropy, and applied Cochran’s Q test for assessing the heterogeneity of our findings. Our investigation identified numerous immune characteristics associated with endometritis. For certain immune traits, a lower risk of endometritis was observed, including: Absolute Counts of CD39 + CD4 + T cells, CD25 + CD39 + CD4 regulatory T cells, and CD25 + + CD8 + T cells; Absolute Counts of Switched Memory B cells; CD19 expression on IgD + CD38dim and Switched Memory B cells; CD20 expression on IgD + CD38− Unswitched Memory B cells; percentage of Switched Memory B cells among lymphocytes; CD16-CD56 expression on HLA DR + Natural Killer cells; percentage of CD11c + CD62L− monocytes; CD86 expression on monocytes; CCR2 expression on CD14 + CD16 + monocytes; and CD14 expression on Monocytic Myeloid-Derived Suppressor Cells, with Odds Ratios (ORs) between 0.413 and 0.703. On the contrary, increased risks of endometritis were linked with: the percentage of Effector Memory CD4 + T cells within the CD4 + T cell population; percentages of HLA DR + T cells and HLA DR + CD8 + T cells among T cells; CD4 expression on CD28 + CD4 + T cells; CD20 expression on CD20- CD38- B cells; percentage of IgD + CD24 + B cells within the B cell population; CD62L expression on CD62L + myeloid Dendritic Cells; and Absolute Counts of Plasmacytoid Dendritic Cells, with ORs from 1.473 to 2.677, indicating these traits potentially elevate the risk of developing endometritis. Our research delineates distinct causal links between specific immune cell phenotypes and endometritis, offering new perspectives that could contribute to the pinpointing of new therapeutic avenues for this condition.

S144: IMMUNE RESTORATION AND SYNERGISTIC ACTIVITY WITH FIRST-LINE (1L) IBRUTINIB (IBR) PLUS VENETOCLAX (VEN): TRANSLATIONAL ANALYSES OF CAPTIVATE PATIENTS WITH CLL

Background: Ibr and Ven work synergistically through their distinct and complementary modes of action: BTK inhibition by Ibr decreases levels of anti-apoptotic MCL-1 and BCL-XL proteins, but not BCL-2, and therefore increases sensitization to BCL-2 inhibition by Ven in vivo. Single agent Ibr has been shown to normalize CLL-associated immune cell alterations in number and function but the impact of the Ibr plus Ven combination (I+V) on immune cells has not been evaluated. Aims: To 1) confirm BCL-2 sensitization by single-agent Ibr and 2) monitor changes in the cellular immune profile of patients (pts) treated with I+V in CAPTIVATE (NCT02910583), a multicenter phase 2 study evaluating 1L I+V treatment (tx) in CLL and SLL. Methods: Ibr (420mg po daily) effects on anti-apoptotic proteins were evaluated by flow cytometry with samples from 4 previously untreated pts with CLL treated for 1 cycle (28 days). Immune restoration was evaluated in 79 previously untreated pts with CLL enrolled in the CAPTIVATE Minimal Residual Disease (MRD) cohort. Pts received 3 cycles of Ibr, followed by 12 cycles of I+V (Ibr 420 mg/d orally; Ven ramp-up to 400 mg/d orally). Pts who met criteria for confirmed undetectable MRD (Confirmed uMRD) were then randomized 1:1 to placebo fixed-duration (FD) tx or Ibr at cycle 16; pts who did not meet Confirmed uMRD criteria (uMRD Not Confirmed) were randomized 1:1 to Ibr or I+V. Cryopreserved peripheral blood mononuclear cells at baseline (pre-dose cycle 1) and day 1 of cycles 4, 7, 16, 20, 23, and 29 in each of the 4 arms were analyzed by high-dimensional flow cytometry (34-color panel). Immune cell subset counts of B cells, T cells, monocytes, dendritic cells (DCs), myeloid-derived suppressor cells, natural killer cells, and innate lymphoid cells were calculated and compared to those of 20 age-matched healthy donors. Median changes from baseline are reported. Results: In pts treated with single-agent Ibr for 1 cycle, MCL-1, BCL-XL and BCL-2 expression decreased by 74%, 95% and 10%, respectively, in lymph node emigrant (CD5+ CXCR4dim) CLL cells, confirming increased BCL-2-dependence and corresponding inhibitor sensitization. In CAPTIVATE pts treated with I+V, a rapid and significant decrease in circulating CLL cells was observed within the first 3 cycles of Ven tx initiation (Fig 1A, cycle 7). From cycle 16 and onwards, Confirmed uMRD pts had CLL cell counts similar to healthy donors (≤0.8 CLL cell/mL), while in uMRD Not Confirmed pts counts were 1.5 to 22.9 CLL cell/mL. Subsequently, normal B-cell count restoration occurred in Confirmed uMRD pts randomized to placebo (FD tx) with a recovery to levels similar to healthy donors (+332% at cycle 29; Fig 1B). Across all arms, abnormal counts of T cell subsets, classical monocytes and conventional DCs characteristic of CLL were normalized to healthy donor levels (‒49%, +101% and +91% respectively) within the first 6 months of tx and were maintained thereafter regardless of randomized tx. Plasmacytoid DCs counts recovered by cycle 20 (+598%) in all 4 arms. Image:Summary/Conclusion: Sensitization to BCL-2 inhibitor effects by Ibr supports the synergistic activity of I+V. The FD regimen (Confirmed uMRD, placebo arm) of I+V effectively eradicated CLL cells to healthy donor levels and enabled sustained regeneration of normal B cell counts in contrast to ongoing therapy in the remaining tx arms. Combination I+V also allowed for normalization of other critical immune cells, including T cell subsets, classical monocytes, and conventional and plasmacytoid DCs. These data demonstrate promising evidence of immune restoration with FD I+V tx.

Impact of Intestinal Microbiota on Reconstitution of Circulating Monocyte, Dendritic Cell, and Natural Killer Cell Subsets in Adults Undergoing Single-Unit Cord Blood Transplantation.

The intestinal microbiota plays a fundamental role in the development of host innate immune cells, such as monocytes, dendritic cells (DCs), and natural killer (NK) cells. We examined the association between intestinal microbiota and subsequent immune reconstitution of circulating monocyte, DC, and NK cell subsets in 38 adult patients undergoing single-unit cord blood transplantation (CBT). A higher diversity of intestinal microbiota at 1 month was significantly associated with higher counts of plasmacytoid DCs at 7 months after CBT, as measured by the Chao1 index. Principal coordinate analysis of unweighted UniFrac distances showed significant differences between higher and lower classical monocyte reconstitution at 7 months post-CBT. The families Neisseriaceae, Burkholderiaceae, Propionibacteriaceae, and Coriobacteriaceae were increased in higher classical monocyte reconstitution at 7 months post-CBT, whereas the family Bacteroidaceae was increased in lower classical monocyte reconstitution at 7 months post-CBT. These data show that intestinal microbiota composition affects immune reconstitution of classical monocyte and plasmacytoid DCs following single-unit CBT.

Low Counts of Plasmacytoid Dendritic Cells after Engraftment Are Associated with High Early Mortality after Allogeneic Stem Cell Transplantation

Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage−; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage−, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.

Higher Counts Of Plasmacytoid Dendritic Cells In The Allograft Are Associated Increased Risk Of Acute Gvhd After Stem Cell Transplantation

Background Recent studies suggest that higher circulating dendritic cell counts after hematopoietic stem cell transplantation (HSCT) may be associated with lower risk of graft versus host disease (GVHD) and mortality. Plasmacytoid dendritic cells (pDC) have tolerogenic properties and may explain such results. However, only a few studies with conflicting results analyzed pDC counts in the allograft, mainly in the related HSCT setting. Objectives To compare pDC counts among different cell sources [umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PBSC)] and to correlate the pDC content on the graft with main HSCT outcomes. Methods Plasmacytoid dendritic cells (pDC: lineage negative, HLA-DR+ and CD123+) were quantified by multiparametric flow cytometry in the graft just before its infusion. Overall, 77 patients (49 male; median age 21y, range 1-74y) receiving UCB (n=26), BM (n=34) or PBSC (n=17) HSCT from unrelated (n=67) or related donors (n=10) were studied. The most common diagnosis was acute leukemia (ALL, 30 cases; AML, 22). Most patients received myeloablative conditioning regimens (n=47, 61%). Antithymocyte globulin was used in 30 patients (39%) and total body irradiation in 41 (53%). Median follow up time was 15 months (4-33). Results Median time to neutrophil engraftment was 19 days (range: 11-49) and 35 days to platelet engraftment (range 2-176). The median percentage of pDC on the graft was 0.20% of non erythroid nucleated cells (range: 0.02-0.67) and no differences were noticed among sources. Cumulative incidence (CI) of grade II-IV acute GVHD at 100 days was higher on patients receiving grafts with higher percentages of pDC (22% for patients with less than 0.15%pDC graft content vs. 52% for patients receiving grafts with higher counts, p=0.026). There was no impact of graft pDC content on mortality, relapse, chronic GVHD or overall survival. In a multivariate analysis, graft pDC content remains an independent risk factor for acute GVHD [HR: 3.0, CI (95%): 1.15-7.8]. Conclusion Higher pDC graft percentages were associated with increased risk of acute GVHD, but had no impact on non-relapse mortality or survival. The precise role of pDC on immunity after HSCT deserves further investigation and might be related not only to pDC biology itself but to the chronology of the pDC interaction with host antigens. Disclosures: No relevant conflicts of interest to declare.

High TNF-alpha and IL-8 levels predict low blood dendritic cell counts in primary cytomegalovirus infection

BackgroundIn vitro studies suggest that human cytomegalovirus (CMV) modulates the functions of dendritic cells (DCs). However, there are limited data on DC homeostasis in CMV-infected patients. ObjectivesThe aim of this study was to characterize circulating DCs and plasma cytokine levels in immunocompetent patients with primary, symptomatic CMV infections. Study designThe study population consisted of 14 patients suffering of CMV mononucleosis and 14 healthy volunteers (11 CMV-seropositive and 3 CMV-seronegative subjects) included as controls. Peripheral blood mononuclear cells were isolated and used to characterize DCs and to quantify CMV in the blood. Plasma levels of pro-inflammatory and anti-inflammatory cytokines were also measured. ResultsWe observed that patients who were developing CMV mononucleosis presented lower myeloid and plasmacytoid DC counts in peripheral blood compared with healthy controls. We also noted elevated levels of inflammatory mediators, of which tumor necrosis factor-α (TNF-α)—which activates DCs and endothelial cells—was the highest. Notably, the decrease in blood DCs correlated with high TNF-α and IL-8 levels by a hyperbolic function. ConclusionsOur results suggest that increased levels of inflammatory factors facilitate alterations in DC homeostasis during primary CMV infection, which may contribute to viral-induced modulation of host immunity.

Low Counts of Plasmacytoid Dendritic Cells After Engraftment Are Associated with Higher Early Transplantation-Related Mortality in Patients Receiving Unrelated HSCT

Abstract 4541 Background:The heterogeneous status of host immune defenses may influence the risk of infection and graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In such defense, dendritic cells (DC) which act as specialized antigen-presenting cells that bridge the innate and adaptive immune systems, and NK-cells, responsible for the innate defense against infections and residual tumor cells, are essential cell components. Objectives:To monitor the recovery of different subsets of DC and NK cells after unrelated umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PBSC) HSCT and to evaluate the impact of the distribution of these cell subsets on the outcome of the transplant. Methods:Overall, 34 patients (median age 13y; range 1–63y) receiving a UCB (n=15), BM (n=14) or PBSC (n=5) unrelated HSCT were studied. The most common diagnosis was acute leukemia (ALL, 12 cases; AML, 10; CML, 5; aplastic anemia, 4; MDS, 2; Hodgkin lymphoma, 1; SCID, 1), a majority of patients were males (56%), and received myeloablative conditioning (MAC) regimens (73%). Antithymocyte globulin (ATG) was used in 38% and total body irraditation (TBI) in 41% of cases. Median time to neutrophil engraftment was 18 days (range: 12–45). T-cell (CD4+, CD8+, CD4−8−, CD4+8+), DC [CD123+ plasmacytoid(p)DC, CD11c+ myeloid(m)DC, and CD16+ monocytoid(mo)DC] and NK cell subsets (CD3−/CD19− 56++16− and 56+16++) were quantified by multiparametric flow cytometry at 7 sequential time points (pre-transplant, at engraftment, and at days 3, 7, 14, 21 and 60 after engraftment). Results: As compared to BM/PBSC, UCB was associated with a delayed neutrophil recovery (28 days vs. 17 days; p=0.01), and a trend to lower counts of all T-, NK- and pDC subsets, particularly for the CD4+ and CD4−/CD8− T-cells during the first 3 weeks after recovery. Conversely, no significant differences were observed between both groups as regards the distribution of mDC and moDC. The use of TBI, MAC or ATG were not associated with the reconstitution of the studied cell subsets. In contrast, patients who died from transplantation-related causes (TRM) had significantly lower counts of pDC and mDC during the first 3 weeks after HSCT. At day 21 after engraftment, the median number of pDC and mDC was 0.9 and 2.0/uL among patients who died from TRM vs. 7.1 (p=.006) and 8.4/uL (p=.01) in the remainder, respectively). Patients presenting grade II-IV acute GVHD also had significantly lower pDC counts at days 14 and 21. There was no significant association of both the hematopoietic stem cell source and the conditioning regimen on the risk of TRM or acute GVHD. Conclusion:Low pDC counts in the first weeks after unrelated HSCT are associated with an increased incidence of GVHD and mortality. The precise mechanisms that might explain the role of pDC on immunity early after HSCT deserve further investigations. Disclosures:No relevant conflicts of interest to declare.

Rapid Disease Progression in HIV-1-Infected Men Who Have Sex with Men Is Negatively Correlated with Peripheral Plasmacytoid Dendritic Cell Counts at the Early Stage of Primary Infection

To explore the relationship between absolute dendritic cell (DC) counts at the early stage of primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) and subsequent disease progression, we performed a prospective study of 16 rapid progressors (RPs) and 12 typical progressors (TPs) from a PHI cohort of men who have sex with men. Significantly decreased plasmacytoid DC (pDC) and myeloid DC (mDC) counts in the blood of RPs were observed at study entry as compared with TPs and healthy HIV-1-negative subjects. Low baseline pDC counts were significantly associated with rapid disease progression after adjustment for baseline CD4(+) T cell counts, mDC counts, and HIV-1 load. Kaplan-Meier survival analysis showed that low pDC counts were strongly associated with rapid disease progression. Our findings demonstrated the predictive value of blood absolute pDC counts at baseline in PHI for HIV-1 disease progression. Further studies are required to confirm this notion.

135 Lower bone marrow myeloid and plasmacytoid dendritic cell counts in high-risk than in low-risk MDS patients and controls

135 Lower bone marrow myeloid and plasmacytoid dendritic cell counts in high-risk than in low-risk MDS patients and controls

Dendritic Cell Count in the Graft Predicts Relapse in Patients with Hematologic Malignancies Undergoing an HLA-Matched Related Allogeneic Peripheral Blood Stem Cell Transplant

We investigated the impact of the number of infused and reconstituted immunocompetent cells including dendritic cells (DCs) on clinical outcome of patients with hematologic malignancies undergoing an allogeneic peripheral blood stem cell transplantation. Sixty-nine consecutive patients with hematologic malignancies were included in the analysis. The median age of the cohort was 32 years (range: 2-62 years) and there were 39 (57%) males. Twenty-one (30%) patients relapsed with a cumulative incidence of 44 % +/- 14% at a median follow up of 28 months. On a multivariate analysis, a high plasmacytoid dendritic cell (PC) content in the graft was associated with higher risk of relapse. The patients were further categorized based on the median PC counts in the graft as high (> or =2.3 x 10(6)/kg) and low (<2.3 x 10(6)/kg) groups. The baseline characteristics of these 2 groups were comparable. The group that had a high PC content in the graft had significantly higher risk of relapse and lower overall survival (OS) and event-free survival (EFS). Our data suggests that PC content in the graft predicts clinical outcomes such as relapse and survival in patients with hematologic malignancies undergoing an allogeneic HLA matched related peripheral blood stem cell transplantation. There is potential for pretransplant manipulation of this cellular subset in the graft.

Differential Effects of P-Class Versus Other CpG Oligodeoxynucleotide Classes on the Impaired Innate Immunity of Plasmacytoid Dendritic Cells in HIV Type 1 Infection

Abstract Human plasmacytoid dendritic cells (PDC) are the major producers of type I interferons (IFN) after stimulation with CpG oligodeoxynucleotides (ODN). HIV-1-infected patients show a deficit in PDC numbers and function with progression of disease. CpG ODN appear to be attractive therapeutics to support the impaired innate immunity in HIV-1 infection. PDC counts, phenotype, and function were analyzed in 23 HIV-infected untreated individuals and 16 controls. Markers for migration (CCR7), activation (CD80), maturation (CD83), and endocytosis (BDCA2) were evaluated at baseline and 20 h after in vitro stimulation with class A, B, C, and P ODN. PDC counts and the expression of BDCA2 on these cells were significantly lower in HIV-1-infected subjects compared to controls (both p < 0.001). After stimulation with CpG ODN, CD80 and CD83 were upregulated to a similar extent in patients and controls, whereas CCR7 was upregulated more efficiently by CpG-P and CpG-C than CpG-A in HIV-1-infected individuals compared to controls. The IFN-alpha induction significantly differed for the CpG ODN classes (A > P > C > B) in patients and controls (p < 0.05). Functional PDC deficits in IFN-alpha and TNF-alpha induction were particularly evident in subjects with less than 500 CD4(+) cells/mul. CpG-P ODNs not only induced remarkable IFN-alpha production in patient PBMCs, but also significantly upregulated the antibacterial and antiviral CXC chemokine IP-10. In conclusion, PDC counts, phenotype, and function are significantly impaired in HIV-1-infected subjects. Optimized P-class ODN may be effective in reversing this innate immune defect, which should be further evaluated in vivo.

Impaired Peripheral Blood Dendritic Cell Counts in B-Chronic Lymphocytic Leukaemia.

B-cell chronic lymphocytic leukaemia (B-CLL) is the most common leukaemia of adults in Western worls accounting for about 40% of leukemias in adults over the age of 65 years. Although, B-CLL cells can, under certain conditions, act as antigen presenting cell (APCs) they fail to generate an efficient anti-leukemic immune response. Dendritic cells (DCs) represent the most potent APCs and they are the only cell type capable of initiating a primary immune response. To asses a potential role of DCs compartment in insufficient anti-leukemic and anti-infectious immunity in B-CLL, we have analysed peripheral blood DCs subsets in 17 patients with an early stage B-CLL and 8 age matched controls by multi colour flow cytometry. Dendritic cells were identified by lack of B, T, NK and monocyte markers, HLA-DR expression and expression of CD11c and CD123 for myeloid and plasmacytoid DCs, respectively. We found a significant reduction of absolute plasmacytoid DCs counts in patients with B-CLL (average count = 49,4×106/L) when compared to healthy donors (average count = 111,3 ×106/L, p<0,05). Myeloid DCs counts were not different from healthy controls (average count = 192,7×106/L vs. 196,7×106/L p=NS). Number of plasmacytoid DCs decreased with B-CLL cells number. DC counts did not depend on CD38 or ZAP70 expression or immunoglobulin mutational status. Phenotypic analysis of circulating plasmacytoid and myeloid DCs showed low co-stimulation profile comparing to isotype controls. Thus, the depletion of pDCs in B-CLL could represent a mechanism contributing to the poor anti-leukemic immune responses in B-CLL and/or to immune deficiency in CLL patients.

Type I Interferon Production Is Profoundly and Transiently Impaired in Primary HIV‐1 Infection

Successful immunological control of human immunodeficiency virus (HIV) infection is achieved only in rare individuals. Plasmacytoid dendritic cells (DCs) are mostly responsible for the production of strong antiviral factors--that is, type I interferons (IFNs)--in response to viruses. Their natural IFN production is impaired in chronic HIV infection, in correlation with viral load and disease progression, but it has not been tested during the critical stage of primary infection, when a balance is set between host immune responses and viral replication. We longitudinally studied 26 patients during the primary stage of HIV infection. Fifteen patients received highly active antiretroviral therapy (HAART) for 12 months. At the time of inclusion into the cohort, median type I IFN production in response to herpes simplex virus type 1 stimulation was dramatically impaired in peripheral blood mononuclear cells (PBMCs) from HIV-infected patients, compared with that in PBMCs from 31 uninfected donors (180 vs. 800 IU/mL; P<.0001). Median circulating plasmacytoid DC counts were also significantly decreased (7300 vs. 13,500 cells/mL; P=.001). Twelve months later, IFN production returned to normal, and the data suggest that HAART may help in the recovery of IFN production by plasmacytoid DCs. These data underline the potential for early antiretroviral treatment and IFN- alpha treatment to enhance viral control in a larger proportion of patients during the critical stage of primary infection.

Plasmacytoid Dendritic Cell Reconstitution Following Bone Marrow Transplantation: Subnormal Recovery and Functional Deficit of IFN-α/β Production in Response to Herpes Simplex Virus

Infections with herpesviruses were frequent after bone marrow transplantation (BMT) before the preventive use of antiviral drugs, suggesting a deficit of innate immunity. A retrospective phenotypical and functional study was carried out on 25 patients 1-36 months after allogeneic BMT. Leukocyte counts followed a normal reconstitution, including natural killer (NK) cells and monocytes. Plasmacytoid dendritic cell (PDC) counts increased steadily, although they remained below normal values after 2 years. Most patients produced less interferon- alpha/beta (IFN-alphabeta) in vitro than healthy controls after infection with herpes simplex virus type 1 (HSV-1), whereas they responded normally to Sendai virus (SV). In addition, 6 patients had biologic signs of infection with herpesviruses, confirming a specific immunologic deficit against these viruses. IFN production was not correlated to PDC counts or to the occurrence of graft-versus-host disease (GVHD). Because all patients were under immunosuppressive treatment, we investigated the effect of drugs on IFN production by mononuclear cells. Glucocorticoids and cyclosporine A inhibited IFN production by infected leukocytes, with a predominant action on HSV-1-infected PDC. The inability of transplanted patients to mount an efficient immune response to herpesviruses may be partly related to drug toxicity toward cells of the innate immune system.

Circulating dendritic cell subset levels after allogeneic stem cell transplantation in children correlate with time post transplant and severity of acute graft-versus-host disease

We examined the recovery of circulating monocytoid (Lin- CD11+ HLA-DR+) and plasmacytoid (Lin- CD123+ HLA-DR+) precursor (pre) dendritic cell (DC) subsets after allogeneic stem cell transplantation (SCT) in 39 children, using age-matched healthy children as controls. The frequencies of DCs in peripheral blood samples were determined by flow cytometry. The initial recovery of DC occurred simultaneously with myeloid engraftment. However, with time, DC subset values declined, being very low 40-50 days after SCT. Low monocytoid and plasmacytoid DC values were associated significantly with the development of severe acute graft-versus-host disease (aGVHD) (P=0.042 and 0.017, respectively). Plasmacytoid DC values were lower than in the age-matched controls for the entire follow-up period (range 102-2569 days), although, with time, values approached normal levels. Normal monocytoid DC numbers were observed within 300-400 days post SCT. The severity of chronic GVHD did not correlate with quantitative recovery of DC. We conclude that in pediatric SCT, initial recovery of DC production is concurrent with that of myelopoiesis, yet with time, DC subset values decline and low counts are associated with severe aGVHD. Monocytoid DC numbers approach normal levels within a year of SCT, but plasmacytoid DC counts recover very slowly.