Soluble Activation Markers Research Articles

Biofilm-dispersed pneumococci induce elevated leukocyte and platelet activation.

Streptococcus pneumoniae (the pneumococcus) effectively colonizes the human nasopharynx, but can migrate to other host sites, causing infections such as pneumonia and sepsis. Previous studies indicate that pneumococci grown as biofilms have phenotypes of bacteria associated with colonization whereas bacteria released from biofilms in response to changes in the local environment (i.e., dispersed bacteria) represent populations with phenotypes associated with disease. How these niche-adapted populations interact with immune cells upon reaching the vascular compartment has not previously been studied. Here, we investigated neutrophil, monocyte, and platelet activation using ex vivo stimulation of whole blood and platelet-rich plasma with pneumococcal populations representing distinct stages of the infectious process (biofilm bacteria and dispersed bacteria) as well as conventional broth-grown culture (planktonic bacteria). Flow cytometry and ELISA were used to assess surface and soluble activation markers for neutrophil and monocyte activation, platelet-neutrophil complex and platelet-monocyte complex formation, and platelet activation and responsiveness. Overall, we found that biofilm-derived bacteria (biofilm bacteria and dispersed bacteria) induced significant activation of neutrophils, monocytes, and platelets. In contrast, little to no activation was induced by planktonic bacteria. Platelets remained functional after stimulation with bacterial populations and the degree of responsiveness was inversely related to initial activation. Bacterial association with immune cells followed a similar pattern as activation. Differences in activation of and association with immune cells by biofilm-derived populations could be an important consideration for other pathogens that have a biofilm state. Gaining insight into how these bacterial populations interact with the host immune response may reveal immunomodulatory targets to interfere with disease development.

Decreased adhesion to endothelium leads to elevated neutrophil granulocyte count in hereditary angioedema patients

As many aspects of hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency (C1-INH-HAE) cannot be explained with elevated bradykinin level alone, it has recently become clear that other factors also play an important role in the pathogenesis. One of these factors could be elevated neutrophil granulocyte (NG) counts, which are associated with increased NG activation in C1-INH-HAE patients; however, their origin has not been elucidated so far. Here, we aimed to investigate whether the excess of NGs is due to disturbed maturation, biased circulating/marginated pool equilibrium or decreased elimination. We enrolled 20 attack-free C1-INH-HAE patients together with 21 healthy controls and collected blood samples. We compared cell surface maturation markers, adhesion molecules, cytokine receptors, and Ca2+-mobilization of NG by flow cytometry, activation markers by ELISA, and NG/endothelial cell adhesion by automated pipetting system. Cell-surface markers showed normal maturation of NGs in C1-INH-HAE patients. Adhesion of NGs to endothelial cells pretreated with lipopolysaccharide or phorbol 12-myristate 13-acetate was significantly weaker in samples from C1-INH-HAE patients and bradykinin had no effect on the adhesion. NGs from C1-INH-HAE patients were in an activated state when assessed by soluble activation markers without any stimulation. Our data support that the maturation of NGs in C1-INH-HAE patients is normal, whereas adhesion properties of patient-derived NGs to the endothelium are reduced compared to those from healthy controls, indicating a bias between the circulating and marginated pools of NGs in patients. Bradykinin may not be responsible for reduced adhesion properties of NGs.

High fragmentation in platelet concentrates impacts the activation, procoagulant, and aggregatory capacity of platelets

Platelets are transfused to patients to prevent bleeding. Since both preparation and storage can impact the hemostatic functions of platelets, we studied platelet concentrates (PCs) with different initial composition in regard to platelet fragmentation and its impact on storage-induced changes in activation potential. Ten whole blood derived PCs were assessed over 7 storage days. Using flow cytometry, platelet (CD41+) subpopulations were characterized for activation potential using activation markers (PAC-1, P-selectin, and LAMP-1), phosphatidylserine (Annexin V), and mitochondrial integrity (DiIC1(5)). Aggregation response, coagulation, and soluble activation markers (cytokines and sGPVI) were also measured. Of the CD41+ events, the PCs contained a median of 82% normal-sized platelets, 10% small platelets, and 8% fragments. The small platelets exhibited procoagulant hallmarks (increased P-selectin and Annexin V and reduced DiIC1(5)). Normal-sized platelets responded to activation, whereas activation potential was decreased for small and abolished for fragments. Five PCs contained a high proportion of small platelets and fragments (median of 28% of CD41+ events), which was significantly higher than the other five PCs (median of 9%). A high proportion of small platelets and fragments was associated with procoagulant hallmarks and decreased activation potential, but, although diminished, they still retained some activation potential throughout 7 days storage.

Innate immune deficiencies are associated with severity and poor prognosis in patients with COVID-19

COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.

Soluble markers of neutrophil, T-cell and monocyte activation are associated with disease severity and parasitemia in falciparum malaria

BackgroundThe immune response during P. falciparum infection is a two-edged sword, involving dysregulation of the inflammatory responses with several types of immune cells participating. Here we examined T-cell, monocyte/macrophage and neutrophil activation during P. falciparum infection by using soluble activation markers for these leukocyte subsets.MethodsIn a prospective cross-sectional study clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) co-infection with HIV-1, as well as HIV-infected patients with similar symptoms but without malaria (n = 58) and healthy controls (n = 52). Soluble (s)CD25, sCD14, sCD163 and myeloperoxidase (MPO) as markers for T-cell, monocyte/macrophage and neutrophil activation, respectively as well as CX3CL1, granzyme B and TIM-3 as markers of T-cell subsets and T-cell exhaustion, were analyzed.ResultsAll patient groups had raised levels of activation markers compared with healthy controls. Levels of sCD25 and MPO increased gradually from patient with HIV only to patient with malaria only, with the highest levels in the HIV/malaria group. In the malaria group as a whole, MPO, sCD14 and in particular sCD25 were correlated with disease severity. sCD163, sCD25 and in particular MPO correlated with the degree of parasitemia as assessed by qPCR. Patients with falciparum malaria also had signs of T-cell subset activation (i.e. increased granzyme B and CX3CL1) and T-cell exhaustion as assessed by high levels of TIM-3 particularly in patients co-infected with HIV.ConclusionOur data support a marked immune activation in falciparum malaria involving all major leukocyte subsets with particular enhanced activation of neutrophils and T-cells in patients co-infected with HIV. Our findings also support a link between immune activation and immune exhaustion during falciparum malaria, particularly in relation to T-cell responses in patients co-infected with HIV.

A Low Frequency of IL-17-Producing CD8+ T-Cells Is Associated With Persistent Immune Activation in People Living With HIV Despite HAART-Induced Viral Suppression

Immune activation is the hallmark of HIV infection, even in patients with highly active anti-retroviral therapy (HAART)-induced viral suppression. A major cause of immune activation during HIV infection is the intestinal microbial translocation as a consequence, among other factors, of the decrease and/or dysfunction of interleukin (IL)-17-producing T-cells, due to their role promoting the integrity of the intestinal barrier. A population of IL-17-producing CD8+ T-cells (Tc17 cells), characterized by the expression of CD161, has been described, but its relation with the persistent immune activation in non-viremic people living with HIV (PLWH) on HAART is unclear. By flow cytometry, we characterized the activation phenotype (evaluated by the expression of HLA-DR and CD38) of circulating CD161-expressing CD8+ T-cells; in addition, we explored the functionality of polyclonally-stimulated Tc17 cells in PLWH under HAART-induced viral suppression, and in healthy individuals. Finally, we determined the association of Tc17 cells with the expression of cellular and soluble activation markers. Circulating CD161-expressing CD8+ T-cells were decreased in PLWH compared with healthy individuals, despite their similar basal activation state. After polyclonal stimulation, IL-17 production was higher in CD8+ T-cells co-expressing HLA-DR and CD38 in healthy individuals. In contrast, although PLWH had a higher frequency of HLA-DR+ CD38+ CD8+ T-cells after stimulation, they had a lower production of IL-17. Interferon (IFN)-γ-producing CD8+ T-cells (Tc1 cells) were increased in PLWH. The low Tc17 cells response was associated with a high expression of CD38 and programmed death 1 protein, high levels of soluble CD14 and the treatment duration. Finally, to explore potential immunomodulatory strategies, the in vitro effect of the anti-inflammatory agent sulfasalazine was assessed on Tc17 cells. Interestingly, a decreased inflammatory environment, death of activated CD8+ T-cells, and an increased frequency of Tc17 cells were observed with sulfasalazine treatment. Thus, our findings suggest that activated CD8+ T-cells have a marked capacity to produce IL-17 in healthy individuals, but not in PLWH, despite HAART. This dysfunction of Tc17 cells is associated with the persistent immune activation observed in these patients, and can be partially restored by anti-inflammatory agents.

Cytochrome c and resveratrol preserve platelet function during cold storage

Donated platelets are stored at 22°C and discarded within 5 days because of diminished function and risk of bacterial contamination. Decline of platelet function has been attributed to decreased mitochondrial function and increased oxidative stress. Resveratrol (Res) and cytochrome c (Cyt c), in combination with hypothermic storage, may extend platelet viability. Platelets from 20 donors were pooled into four independent sets and stored at 22°C or 4°C in the absence or presence of Res (50 μM) or Cyt c (100 μM) for up to 10 days. Sequential measurement of platelet counts, coagulation function (thromboelastography), oxygen consumption, lipid peroxidation, glucose-lactate levels, pH, TCO2, and soluble platelet activation markers (CD62P/PF-4) was performed. Platelet function diminished rapidly over time at 22°C versus 4°C (adenosine diphosphate, day 10 [0.6 ± 0.5] vs. [7.8 ± 3.5], arachidonic acid: day 10 [0.5 ± 0.5] vs. [30.1 ± 27.72]). At 4°C, storage treatment with Res or Cyt c limited deterioration in platelet function up to day 10, an effect not observed at 22°C (day 10, 4°C, Con [7.8 ± 3.5] vs. Res [37.3 ± 24.19] vs. Cyt c [45.83 ± 43.06]). Mechanistic analysis revealed oxygen consumption increased in response to Cyt c at 22°C, whereas neither Cyt c or Res affected oxygen consumption at 4°C. Lipid peroxidation was only reduced at 22°C (day 7 and day 10), but remained unchanged at 4°C, or when Res or Cyt c was added. Cytosolic ROS was significantly reduced by pretreatment with Res at 4°C. Total platelet count and soluble activation markers were unchanged during storage and not affected by Res, Cyt c, or temperature. Glucose concentration, pH and TCO2 decreased while lactate levels increased during storage at 22°C but not 4°C. Platelet function is preserved by cold storage for up to 10 days. This function is enhanced by treatment with Res or Cyt c, which supports mitochondrial activity, thus potentially extending platelet shelf life.

Stability of cytokines, chemokines and soluble activation markers in unprocessed blood stored under different conditions

BackgroundBiomarkers such as cytokines, chemokines, and soluble activation markers can be unstable when processing of blood is delayed. The stability of various biomarkers in serum and plasma was investigated when unprocessed blood samples were stored for up to 24h at room and refrigerator temperature. MethodsBlood was collected from 16 healthy volunteers. Unprocessed serum, EDTA and heparinized blood was stored at room (20–25°C) and refrigerator temperature (4–8°C) for 0.5, 2, 4, 6, 8, and 24h after collection before centrifugation and separation of serum and plasma. Samples were batch tested for various biomarkers using commercially available immunoassays. Statistically significant changes were determined using the generalized estimating equation. ResultsIFN-γ, sIL-2Rα, sTNF-RII and β2-microglobulin were stable in unprocessed serum, EDTA and heparinized blood samples stored at either room or refrigerator temperature for up to 24h. IL-6, TNF-α, MIP-1β and RANTES were unstable in heparinized blood at room temperature; TNF-α, and MIP-1β were unstable in unprocessed serum at room temperature; IL-12 was unstable in unprocessed serum at refrigerator temperature; and neopterin was unstable in unprocessed EDTA blood at room temperature. IL-1ra was stable only in unprocessed serum at room temperature. ConclusionAll the biomarkers studied, with the exception of IL-1ra, were stable in unprocessed EDTA blood stored at refrigerator temperature for 24h. This indicates that blood for these biomarkers should be collected in EDTA and if delays in processing are anticipated the unseparated blood should be stored at refrigerator temperature until processing.

Markers of platelet activation are increased in adolescents with type 2 diabetes.

In adults with diabetes, in vivo platelet activation is a marker for atherosclerosis and cardiovascular disease (CVD). This pilot study investigated whether adolescents with diabetes had evidence of increased in vivo platelet activation. In vivo platelet activation was compared in four groups of age-matched adolescents: type 1 diabetes (T1D, n = 15), type 2 diabetes (T2D; n = 15), control subjects with normal BMI (n = 14), and overweight/obese control subjects (n = 13). Platelet surface activation markers and plasma levels of soluble activation markers were measured and compared among groups. Increased expression of all activation markers was observed in T2D compared with either control group (P < 0.05); levels of soluble markers were also higher in T2D than in T1D (P < 0.05). There were no differences in marker expression between the nondiabetic control groups. Platelet activation in adolescents with T2D may be a marker for the risk of CVD development in early adulthood.

A rapid flow cytometric technique for the detection of platelet‐monocyte complexes, activated platelets and platelet‐derived microparticles

Platelet activation occurs in a variety of clinical situations in which it directly contributes to the pathology. This study reports a simple flow cytometric assay for platelet activation which measures platelet-derived microparticles, activated platelets and platelet-monocyte complexes. Pre- and post analytical conditions were investigated and optimized and a normal range established on 20 healthy controls. Twenty patients pre- and post percutaneous coronary intervention (PCI) were tested with the technique. Soluble activation markers sCD40 ligand and sP-selectin and plasma phospholipid levels were measured in both groups. There was a significant increase in activated platelets and platelet-monocyte complexes between normal and pre-PCI (P = 0.005 and 0.0275, respectively) suggesting an activated state. There was a significant fall in activated platelets post-PCI (P = 0.0027) which was mirrored by a fall in soluble CD40 ligand, soluble P-selectin and plasma phospholipid levels (P = 0.0066, <0.0001 and 0.0032, respectively) consistent with antiplatelet therapy administered during the process. This is a reliable and rapid method for the assessment of ex vivo platelet activation which may be an aid in diagnosis and help guide therapy for patients with thrombotic disease.

P.2.096 No association between serotonin transporter polymorphism and schizophrenia

Objective: To search for evidence of immune activation in idiopathic preterm term labour by measuring the soluble markers of T cell activation, CD8 (sCD8) and interleukin-2 receptor (sIL2R). Design: Serum sCD8 and sIL-2R were measured by commercial ELISA in subjects undergoing idiopathic preterm labour (PTL; n = 15) and normal term labour (TL; n = 17). Two gestationally equivalent non-labouring groups were also included representing preterm (PTC; n = 10) and term (TC; n = 10) controls. Possible delayed responses in soluble activation markers were monitored in blood samples taken 48 h after delivery in both labouring groups (PTLp; n = 9: TLp; n = 9). Results: (1) Excluding the 48 h postpartum samples, no statistically significant differences were revealed following a Kruskall-Wallis analysis of variance (ANOVA) for levels of sIL-2R (P = 0.093) and sCD8 (P = 0.098). Including the postpartum samples, however, gave statistically significant differences for each (sIL-2R: P = 0.033; sCD8: P = 0.006). (2) No statistically significant difference was revealed by direct comparison of the two labouring groups alone (Wilcoxon-Mann-Whitney test: P > 0.05). (3) Significantly lower levels of sCD8 were found in the PTL subgroup which had histological evidence of inflammation (Wilcoxon-Mann-Whitney: P = 0.003). Conclusions: Statistical analysis of our data suggests that idiopathic preterm labour is not commonly associated with significant elevations in circulating sCD8 or sIL-2R levels compared with normal term labour. Where significant changes in the levels of these markers do arise, our evidence points to a delayed effect of labour per se rather than infection as the most probable cause.

Quality assessment of heparin coatings by their binding capacities of coagulation and complement enzymes.

In vitro testing of blood contacting materials before clinical application is generally advisable. Four heparin coatings from different manufacturers were tested for adsorbed proteins and soluble activation markers. The surface with the highest antithrombin, thrombin, high-molecular-weight-kininogen (HMWK) and the lowest fibrinogen binding capacity (Carmeda, Medtronic) showed significantly lower levels of granulocytes and platelet activation (beta-TG, PMN-elastase release). No statistically significant differences in soluble markers of the coagulation system could be detected (F1 + 2, TAT). Interestingly, complement activation (TCC) was significantly reduced within the group of the lowest adsorption of the complement factor C3. Our data demonstrate that there is a relation between the binding affinity of proteins (C1-inhibitor, C3-complement) and the consecutive changes in complement activation (TCC). Therefore, measuring adsorbed proteins on artificial surfaces is a suitable, sensitive and very reproducible method for assessing the thrombogenicity of biomaterials.

Differential B- and T-cell activation in Wegener’s granulomatosis

Background: Autoimmune mechanisms are postulated to play a role in the development and progression of Wegener’s granulomatosis (WG), a form of systemic, idiopathic necrotizing vasculitis. Objective: We investigated the relation between lymphocyte activation and disease activity in patients with WG. Methods: B- and T-lymphocyte activation was studied by cytometric assessment of the expression of the activation markers CD38 on B cells and CD25 and HLA-DR on CD4 + and CD8 + T-cell subsets, respectively. Activation at the cellular level was related to serum levels of antineutrophil cytoplasmic antibodies and soluble IL-2 receptor, which can be regarded as soluble activation markers of B and T cells. Results: Percentages of CD38 bright activated B cells were higher in patients with active WG than in patients experiencing disease remission ( P < .05) or in healthy control subjects ( P < .05). Percentages of activated CD4 + and CD8 + T cells were higher in patients with active WG (CD4 subset, P < .0001; CD8 subset, P < .005) than in healthy individuals. An increased percentage of activated T cells of both subsets was also seen in patients whose condition was in remission, as compared with healthy control subjects (CD4 subset, P < .0005; CD8 subset, P < .001). Lymphocyte activation at the cellular level did not correlate with plasma levels of antineutrophil cytoplasmic antibodies or soluble IL-2 receptor. Conclusion: In WG, B-cell activation is related to active disease, whereas T-cell activation persists during remission of the disease, which points to an intrinsic disordered immune system in this disease. (J Allergy Clin Immunol 1999;103:885-94.)

Stability of plasma levels of cytokines and soluble activation markers in patients with human immunodeficiency virus infection.

Cytokine and immune activation marker levels in plasma are valuable measurements of immune status and treatment effects in human immunodeficiency virus (HIV) infection and AIDS. Five populations representing various stages of disease were studied: controls, 2 AIDS groups with <50/mm3 CD4 cells, and 2 groups of HIV-positive subjects-1 with stable CD4 T cells (median, 545/mm3) and 1 with >100/mm3 CD4 cell decline in 1 year. Relatively stable levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor (R)II, soluble interleukin-2R, neopterin, and beta2-microglobulin (beta2M) were documented over 5-8 weeks in patients with AIDS and for 1-4 years in the other groups. beta2M was generally the most stable marker. Interferon-gamma levels, however, fluctuated substantially. Individuals, whether normal or HIV-positive, maintain characteristic plasma levels of cytokines and immune activation markers. Thus, documented changes, in excess of the variability observed in this study, are likely to be significant indicators of change in disease status or effects of therapy.

Psoriasis: comparison of immunological markers in patients with acute and remission phase

The immune system involvement in psoriasis has been documented by the presence of activated T-cells both in peripheral blood and in psoriatic skin lesions and by the intervention of cytokines in the inflammatory process. On this basis, we have undertaken a study in order to examine, in addition to activation markers such as CD25 and CD54 (ICAM-1) on peripheral blood mononuclear cells (PBMNCs) surface, serum levels of soluble interleukin (IL)-2 receptor (sIL-2R), soluble ICAM-1 (sICAM-1), soluble CD4 (sCD4), soluble CD8 (sCD8), β2-microglobulin and fibronectin (FN) in psoriatic patients analyzed both in acute and remission phase obtained by topical therapy alone. Our results show that PBMNCs expressing IL-2 receptor (CD25) were increased both in percentage and absolute number in respect to controls, and were not modified after remission. On the contrary, the significantly higher number of CD54 + lymphocytes evaluated in acute psoriasis, showed a reduction during the remission phase, even if the values persisted higher than controls. Serum levels of sIL-2R, sICAM-1, sCD4, sCD8 and β2-microglobulin were significantly higher than controls both in acute and remission phase; only FN levels were found to be lower, in patients evaluated both in acute psoriasis and after therapy, in respect to normal donors. On the whole, these results seem to indicate the persistence of both cellular and soluble activation markers even in psoriasis remission phase; in this light, we can suppose that topical therapy alone is not able to efficiently down-regulate activation mechanisms involved in the pathogenesis of the disease.

Cell-mediated immunity in patients with head-neck carcinoma

The immune system involvement in psoriasis has been documented by the presence of activated T-cells both in peripheral blood and in psoriatic skin lesions and by the intervention of cytokines in the inflammatory process. On this basis, we have undertaken a study in order to examine, in addition to activation markers such as CD25 and CD54 (ICAM-1) on peripheral blood mononuclear cells (PBMNCs) surface, serum levels of soluble interleukin (IL)-2 receptor (sIL-2R), soluble ICAM-1 (sICAM-1), soluble CD4 (sCD4), soluble CD8 (sCD8), β2-microglobulin and fibronectin (FN) in psoriatic patients analyzed both in acute and remission phase obtained by topical therapy alone. Our results show that PBMNCs expressing IL-2 receptor (CD25) were increased both in percentage and absolute number in respect to controls, and were not modified after remission. On the contrary, the significantly higher number of CD54+ lymphocytes evaluated in acute psoriasis, showed a reduction during the remission phase, even if the values persisted higher than controls. Serum levels of sIL-2R, sICAM-1, sCD4, sCD8 and β2-microglobulin were significantly higher than controls both in acute and remission phase; only FN levels were found to be lower, in patients evaluated both in acute psoriasis and after therapy, in respect to normal donors. On the whole, these results seem to indicate the persistence of both cellular and soluble activation markers even in psoriasis remission phase; in this light, we can suppose that topical therapy alone is not able to efficiently down-regulate activation mechanisms involved in the pathogenesis of the disease.

Maternal levels of serum-soluble CD8 and IL-2R are not significantly elevated in idiopathic preterm labour

Objective: To search for evidence of immune activation in idiopathic preterm term labour by measuring the soluble markers of T cell activation, CD8 (sCD8) and interleukin-2 receptor (sIL2R). Design: Serum sCD8 and sIL-2R were measured by commercial ELISA in subjects undergoing idiopathic preterm labour (PTL; n = 15) and normal term labour (TL; n = 17). Two gestationally equivalent non-labouring groups were also included representing preterm (PTC; n = 10) and term (TC; n = 10) controls. Possible delayed responses in soluble activation markers were monitored in blood samples taken 48 h after delivery in both labouring groups (PTLp; n = 9: TLp; n = 9). Results: (1) Excluding the 48 h postpartum samples, no statistically significant differences were revealed following a Kruskall-Wallis analysis of variance (ANOVA) for levels of sIL-2R ( P = 0.093) and sCD8 ( P = 0.098). Including the postpartum samples, however, gave statistically significant differences for each (sIL-2R: P = 0.033; sCD8: P = 0.006). (2) No statistically significant difference was revealed by direct comparison of the two labouring groups alone (Wilcoxon-Mann-Whitney test: P > 0.05). (3) Significantly lower levels of sCD8 were found in the PTL subgroup which had histological evidence of inflammation (Wilcoxon-Mann-Whitney: P = 0.003). Conclusions: Statistical analysis of our data suggests that idiopathic preterm labour is not commonly associated with significant elevations in circulating sCD8 or sIL-2R levels compared with normal term labour. Where significant changes in the levels of these markers do arise, our evidence points to a delayed effect of labour per se rather than infection as the most probable cause.

Humoral immune responses in human HIV-1 infection clearance of initial burst of virus replication and protection against disease progression.

An attempt is made to summarize the evidence that humoral immune responses in natural HIV-1 infection play a role in clearance of the initial burst of replication as well as in protection against rapid disease progression. Therefore, the so-called "asymptomatic carrier state" was defined on the basis of immunological characteristics, such as CD4+ cell number, CD45RA-CD29+ cell number, CD4+ proliferative responses to anti-CD3 mAbs and soluble activation markers, as well as virological characteristics such as the state of the viral genome in the cell, levels of genomic RNA production, antigenemia, viremia and virus phenotype. During natural infection two major classes HIV-1 neutralizing and cell-fusion inhibiting antibodies are elicited. One population directed against mostly continuous epitopes localized in the third variable domain (V3) of the envelope and one against discontinuous epitopes of the envelope. The last population blocks gp120-CD4 attachment, the first does not. The role of each of these populations of functional antibodies, in the clearance of viremia and the maintenance of the asymptomatic carrier state is discussed.