Naive Helper Research Articles

Development of Lymphocyte Subpopulations in Preterm Infants

In preterm neonates the immune system is thought to be less developed at birth, but very little is known about the actual size of lymphocyte subpopulations, and even less about the maturation of these subpopulations during the first months after a premature birth. To evaluate the development of lymphocyte subpopulations in preterm infants during the first 3 months after birth, we performed a prospective longitudinal study in two hospitals in the Netherlands. Preterm neonates (n = 38) of all post-menstrual ages were included and blood samples were taken from cord blood, and at 1 week, 6 weeks, and 3 months. Lymphocyte subpopulations were measured by four-colour flow cytometry. The data were compared with follow-up data obtained in healthy term neonates (n = 8), and with single samples from school age children (n = 5) and adults (n = 5). Overall, we found a similar pattern of post-natal development of lymphocyte subpopulations in the term and preterm infants. Both B lymphocytes and helper and cytotoxic T lymphocytes mainly consist of naive cells at birth and during the 3 months of follow-up in all neonatal age groups. So, the preterm immune system seems to be able to generate an outburst of naive T and B lymphocytes from the thymus and bone marrow within the same time span after the start of post-natal antigenic stimulation from the environment as the term immune system, but, with lower post-menstrual age, the absolute counts of naive helper T lymphocytes are lower.

Plasma cells negatively regulate the follicular helper T cell program

B lymphocytes differentiate into antibody-secreting cells under the antigen-specific control of follicular helper T (TFH) cells. Here, we demonstrate that isotype-switched plasma cells expressed MHCII, CD80 and CD86 and intracellular machinery required for antigen presentation. Antigen-specific plasma cells could access, process and present sufficient antigen in vivo to induce multiple TH cell functions. Importantly, antigen-primed plasma cells failed to induce interleukin 21 or Bcl-6 in naïve TH cells and actively shut down these key molecules in antigen-activated TFH cells. Mice lacking plasma cells displayed altered TFH activity, providing evidence for this negative feedback loop. Hence, antigen presentation by plasma cells defines a new layer of cognate regulation that limits the antigen-specific TFH program controlling ongoing B cell immunity.

Both Normal Memory Counts and Decreased Naive Cells Favor Intrinsic Defect Over Early Senescence of Down Syndrome T Lymphocytes

Because of their increased malignancies, autoimmune diseases, and infections, patients with Down syndrome (DS) show features of immunodeficiency. The DS thymus and T lymphocyte subsets have indeed proven to be different, and this has been interpreted as precocious aging. Our study on T lymphocyte subpopulations in DS shows that the normal expansion of naive helper (CD4CD45RA) and cytotoxic (CD8CD45RACD27) T lymphocytes is lacking in the first years of life; this is more logically explainable with an intrinsic T lymphocyte defect. Furthermore, memory cell numbers are not different from age-matched controls (AMC), which does not support the hypothesis of precocious aging. Although the absolute numbers of T lymphocyte subpopulations approach AMC levels toward adulthood, the persistent clinical problems suggest that these cells may not function optimally. However, the clinical picture does not fit severe T lymphocyte deficiency. The latter concept is also supported by our finding that cytomegalovirus (CMV)-seropositive DS children show similar numbers of terminally differentiated cytotoxic T lymphocytes when compared with healthy children, not increased numbers as are seen in immunocompromised hosts.

TH2 bias: Mina tips the balance

Tipping the balance of early cytokine production can lead to lineage bias and, potentially, immune-mediated pathology. Mapping of a leishmania-susceptibility region has identified a gene that may determine the extent of T helper type 2 bias in naive helper T cells.

From the two-dimensional Th1 and Th2 phenotypes to high-dimensional models for gene regulation

The T(h)1/T(h)2 paradigm has been used for decades to characterize phenotypically different immune responses. Recent discoveries, e.g. T(h)17 cells are adding more dimensions to the helper T cell framework, and the T(h)1/T(h)2 paradigm is currently being extended to include these new phenotypes. Previous mathematical models cannot easily be extended to accommodate these new phenotypes, and therefore these discoveries call for a new type of models. We devised a new model of helper T cell differentiation that describes expression of, and interactions between, the master regulators determining the phenotypic polarization of helper T cells. The model is able to describe any number of master regulators and is grounded on transcription factors binding promoter sites and binding each other. The model allows for stable switches between several different phenotypes. Furthermore, the model accounts for the kinetics of FoxP3 and GATA3 mRNA expression measured after stimulating naive helper (CD4+CD45RA+) T cells under various circumstances. Due to its n-dimensional character, this model may easily be applied to other developmental processes that involve master regulators.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs) are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

Neuropilin-1 Expression on Regulatory T Cells Enhances Their Interactions with Dendritic Cells during Antigen Recognition

SummaryThe interaction of T cells with dendritic cells (DCs) determines whether an immune response is launched or not. Recognition of antigen leads to formation of immunological synapses at the interface between the cells. The length of interaction is likely to determine the functional outcome, because it limits the number of MHC class II-peptide complexes that can be recruited into the synapse. Here, we show that regulatory T (Treg) cells and naive helper T (Th) cells interact differently with DCs in the absence of proinflammatory stimuli. Although differences in T cell receptor repertoire might contribute, Foxp3-induced phenotypic differences play a major role. We found that Neuropilin-1 (Nrp-1), which is expressed by most Treg cells but not naive Th cells, promoted prolonged interactions with immature DCs (iDCs), resulting in higher sensitivity to limiting amounts of antigen. This is likely to give Treg cells an advantage over naive Th cells, with the same specificity leading to a “default” suppression of immune responses in the absence of “danger signals.”

Role of IL-6 in the development and pathogenesis of CIA and EAE

Interleukin (IL)-6 is a pleiotropic cytokine that has crucial roles in the regulation of immune response, inflammation and hematopoiesis. Recently, a new inflammatory helper T cell subset which produces IL-17A (IL-17), termed Th17 cells was identified and has been reported to be involved in the development and pathogenesis of collagen induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE), which are known as the mouse model of rheumatoid arthritis and multiple sclerosis, respectively. It has been demonstrated that IL-6 together with TGF-beta induces the differentiation of Th17 cells from naive helper T cells in vitro. However, IL-6 independent pathway of Th17 differentiation has also been reported, suggesting that the role of IL-6 in vivo in these diseases remains unclear. With the treatment of anti-IL-6R antibody in CIA and EAE, we could suppress the differentiation of antigen specific Th17 cells and the onset of diseases. These results indicate that IL-6 is involved in the induction of Th17 cells in vivo, and anti-IL-6R antibody might be a promising therapy of Th17-mediated autoimmune diseases.

An Intact Spleen Is Required for Alloimmunization to Transfused Red Blood Cells Due to Intrasplenic Activation of CD4+ T Cells.

Background: Factors influencing rates of alloimmunization to antigens on transfused red blood cells (RBC alloimmunization) are poorly defined. In particular, the role of the spleen with respect to alloantibody formation is unclear, with conflicting clinical reports in the literature. Moreover, the complexities of multiply mismatched antigens and antigen priming due to transfusions prior to splenectomy make human studies difficult to interpret. To better define the role of the spleen in RBC alloimmunization, we utilized a murine model of transfusion medicine (with the model RBC antigen mHEL (membrane bound hen egg lysozyme)). Methods: Cohorts of splenectomized and non-splenectomized mice (C57BL/6 × B10.BR) were transfused with the human dose equivalent of 1 unit of leukoreduced mHEL RBCs. RBC alloimmunization was assessed by anti-HEL IgG specific ELISA. The role of antigen-specific CD4+ T cells was studied by the adoptive transfer of 1.5 × 106 HEL-specific CFSE-labeled CD4+ T cells from 3A9 TCR transgenic donors. Adoptively transferred cells were visualized using a congenic marker (Thy1.1); enumeration and division of these cells were monitored by flow cytometry in liver, spleen (if applicable), and lymph node preparations. Results: Splenectomy dramatically decreased RBC alloimmunization; 14 of 14 splenectomized mice (from 3 experiments) had undetectable to very low levels of anti-HEL IgG following transfusion with mHEL RBCs (average 6.3 fold less than non-splenectomized mice, 95% C.I. 4.6). Moreover, ten of ten splenectomized mice failed to make detectable levels of anti-HEL IgG even following the adoptive transfer of HEL-specific CD4+ T cells. In comparison, elevating the precursor frequency of HEL-specific CD4+ T cells increased RBC alloimmunization by 10,000 fold in non-splenectomized mice. Proliferation and division of CD4+ T cells were detectable in both spleen and liver preparations of non-splenectomized mice by day 3 following transfusion; in contrast, no expansion nor division of CD4+ T cells was seen in liver nor lymphatic preparations of splenectomized animals. Conclusions: The low level of RBC alloimmunization seen in non-splenectomized mice in this system is limited by existing CD4+ helper T cell responses, as increasing the naive helper T cell precursor frequency dramatically increased RBC alloimmunization. Furthermore, the spleen itself is critical to CD4+ helper T cell function during alloimmunization given that, in splenectomized mice, adoptively transferred HEL-specific CD4+ T cells fail to expand, divide, or stimulate production of detectable alloantibody. Ongoing studies are investigating the phenotype of HEL-specific CD4+ T cells (as effector cells, anergic cells, or regulatory cells) in splenectomized and non-splenectomized mice. These studies have implications for preventing alloimmunization in transfusion-dependent patient populations.

Molecular cloning and expression analysis of T-bet in ginbuna crucian carp (Carassius auratus langsdorfii)

In the adaptive immune system of mammals, naive helper T (Th) cells differentiate into Th1 or Th2 cells. The T-box expressed in T cells (T-bet) is a member of a family of T-box transcription factors that regulates the expression of IFN-γ and plays a crucial role in Th1 cell differentiation and cell-mediated immunity. We cloned and sequenced T-bet cDNA for the first time from non-mammalian species, ginbuna crucian carp. Ginbuna T-bet was composed of 608 predicted amino acids and showed 41.5% identity with human T-bet (Tbx21), and human and ginbuna T-bet share 77.3% identity in their T-box regions. Comparative genomic analysis showed conserved synteny in these regions between zebrafish, fugu, medaka and human T-bet. Phylogenetic analysis indicated that ginbuna T-bet is closely related to that of mouse and human. In unstimulated fish, ginbuna T-bet mRNA was strongly expressed in peripheral blood leukocytes (PBL), head kidney (HK) and spleen. RT-PCR analysis in kidney cells sorted by FACS revealed that T-bet was strongly expressed in surface-IgM-negative lymphocytes in comparison to IgM-positive lymphocytes. These results suggest that ginbuna T-bet is involved in the immune system, especially in T-cell function, and is an important tool to analyze teleost cell-mediated immunity.

In Vitro Model for Modulation of Helper T Cell Differentiation and Activation

Influence of immunotoxicants on helper T cell reactivities can be investigated by assessing acquisition of IL-4- or IFN-γ-producing ability in vitro with antigen-primed naive or precursor helper T cells from the spleens of DO11.10 ovalbumin-specific transgenic mice. The in vitro differentiation model is believed to be close to the in vivo environmental conditions in which differentiation occurs. The effect of immunotoxicants on helper T cell activity can also be evaluated by antigen-specific activation of cloned type-1 or type-2 helper T cells in vitro, since the two subsets of helper T cells can be distinguished by patterns of cytokine secretion. This in vitro model will help investigators to examine the ability of toxicants to modulate helper T cell-mediated cellular or humoral immunity.

Polyacetylenic Compounds and Butanol Fraction fromBidens pilosacan Modulate the Differentiation of Helper T Cells and Prevent Autoimmune Diabetes in Non-Obese Diabetic Mice

Compelling evidence suggests that infiltrating CD4+ type I helper T (Th1) cells in the pancreatic islets play a pivotal role in the progression of diabetes in non-obese diabetic (NOD) mice. We demonstrate in the present report that a butanol fraction of B. pilosa suppressed the development of diabetes, helped maintain levels of blood sugar and insulin in NOD mice in a dose-dependent manner and elevated the serum IgE levels regulated by Th2 cytokines in NOD mice. Moreover, the butanol fraction inhibited the differentiation of naive helper T (Th0) cells into Th1 cells but enhanced their transition into type II helper T (Th2) cells using an in vitro T cell differentiation assay. Two polyacetylenic compounds, 2-beta-D-glucopyranosyloxy-1-hydroxy-5(E)-tridecene-7,9,11-triyne and 3-beta-D-glucopyranosyloxy-1-hydroxy-6(E)-tetradecene-8,10,12-triyne, identified from the butanol fraction also prevented the onset of diabetes like the butanol fraction. The latter compound showed a stronger activity for T cell differentiation than the former. In summary, the butanol fraction of B. pilosa and its polyacetylenes can prevent diabetes plausibly via suppressing the differentiation of Th0 cells into Th1 cells and promoting that of Th0 cells into Th2 cells.

Lymphocyte subsets in healthy children from birth through 18 years of age: The pediatric AIDS clinical trials group P1009 study

Background Peripheral blood lymphocyte subsets need to be determined in a large, urban, minority-predominant cohort of healthy children to serve as suitable control subjects for the interpretation of the appearance of these cells in several disease conditions, notably pediatric HIV-1 infection. Objective We sought to determine the distribution of lymphocyte subsets in healthy urban-dwelling infants, children, and adolescents in the United States. Methods Lymphocyte subsets were determined by means of 3-color flow cytometry in a cross-sectional study of 807 HIV-unexposed children from birth through 18 years of age. Results Cell-surface marker analysis demonstrated that age was an extremely important variable in 24 lymphocyte subset distributions measured as percentages or absolute counts—eg, the CD4 (helper) T cell, CD8 (cytotoxic) T cell, CD19 B cell, CD4CD45RACD62L (naive helper) T cell, CD3CD4CD45RO (memory helper) T cell, CD8HLA-DRCD38 (activated cytotoxic) T cell, and CD8CD28 (activation primed cytotoxic) T cell. The testing laboratory proved to be an important variable, indicating the need for using the same laboratory or group of laboratories to assay an individual's blood over time and to assay control and ill or treated populations. Sex and race-ethnicity were much less important. Conclusion The results of this study provide a control population for assessment of the effects of HIV infection on the normal development and distribution of lymphocyte subsets in children of both sexes, all races, and all ethnic backgrounds from birth through 18 years of age in an urban population. This study's findings will also prove invaluable in interpreting the immune changes in children with many other chronic diseases, such as primary immunodeficiency, malignancy, rheumatoid arthritis, and asthma.

Dendritic Cells and their Potential Therapeutic Role in Haematological Malignancy

The generation of an effective immune response is dependent on the efficient capture and presentation of antigen by antigen-presenting cells. The most potent antigen-presenting cells are dendritic cells (DC). These cells have the capability of activating naive helper and cytotoxic T cells. In recent years it has been demonstrated that in vivo responses to a number of solid tumours can be generated by DC pulsed with either purified tumour antigen or whole tumour cell lysate. In addition, a number of in vivo studies using DC have also been attempted in solid tumours, with some encouraging results. In haematological malignancies, there is now strong evidence that previous T cell anergy can be reversed and significant anti-tumour immune responses generated, in vitro, against the majority of leukaemias. As far as in vivo studies in haematological malignancies are concerned, although T cell responses have been demonstrated in the majority of cases and some dramatic early clinical responses reported, overall results appear disappointing. However, considering the fact that many of these studies were performed in patients with advanced disease and that such therapeutic strategies are still in their infancy, the overall results are actually quite encouraging. Although there is a real potential for DC immunotherapy in the future, it is important to be realistic about the limitations and obstacles to its development. It is highly unlikely that any form of immunotherapy is going to be effective in advanced disease due to the physical bulk of tumour, the immunosuppressive effects of tumours themselves and to any secondary immunosuppression following standard cancer therapy. The potential for immunotherapy is likely to lie either in adjunctive therapy or for treating minimal residual disease. Even in those situations, one of the major obstacles to be overcome is the state of immunological anergy or tolerance that many tumours seem able to induce. Indeed, there is evidence that, under certain circumstances, DC themselves can present antigen in such a way as to produce this state of anergy. Although, in vitro manipulation of DC and T cells can generate tumour-specific T cells from previously "anergic" cells, once reintroduced in vivo, these cells will be re-exposed to the tumour environment with the risk of being rendered anergic again.

Rapid Expansion and IL-4 Expression by Leishmania-Specific Naive Helper T Cells In Vivo

CD4 T cells are pivotal for effective immunity, yet their initial differentiation into effector subsets after infection remains poorly defined. We examined CD4 T cells specific for the immunodominant Leishmania major LACK antigen using MHC/peptide tetramers and IL-4 reporter mice. Comprising ∼15 cells/lymph node in naive mice, LACK-specific T cells expanded over 100-fold, and 70% acquired IL-4 expression by 96 hr. Despite their pathogenic role in susceptible mice, LACK-specific precursor frequency, expansion, and IL-4 expression were comparable between susceptible and resistant mice. When injected with unrelated antigen, Leishmania efficiently activated IL-4 expression from naive antigen-specific T cells. CD4 subset polarization in this highly characterized model occurs independently from IL-4 expression by naive T cells, which is activated indiscriminately after parasitism.

Improved disease-free–survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia

Outcomes after peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (n = 37) were compared with outcomes after bone marrow transplantation (BMT) (n = 54) in the HLA-compatible unrelated donor setting. Median follow-up was 17 months after PBSCT and 29 months after BMT. Both neutrophil and platelet recovery were faster after PBSCT (P <.05). PBSCT was associated with improved immune reconstitution, with higher peripheral blood naive (CD4(+)CD45RA(+)) and memory (CD4(+) CD45RO(+)) helper T cells at 3 months and 12 months after transplantation (P <.03). The cumulative incidence of acute (grades II-IV) and chronic graft-versus-host disease (GVHD) were similar, but BMT was associated with a higher cumulative incidence of severe, acute (grade III-IV) GVHD at 24% as compared with 8% with PBSCT (P <.05). Molecular relapse, defined by 2 consecutive positive polymerase chain reaction assays for bcr-abl within a 4-week interval, occurred in 12 of 45 evaluable patients (27%) after BMT and in 4 of 37 (11%) after PBSCT (not significant). Cytogenetic relapse occurred in 5 of 54 patients after BMT (9%) and in 1 of the 37 (3%) patients after PBSCT (not significant). Seventeen of the 54 patients died after BMT (31%), as compared with 2 of 37 patients after PBSCT (5%). Deaths in the BMT group were associated mainly with infections and severe, acute GVHD. The estimated probability of transplant-related mortality (TRM) and disease-free survival at 1000 days after receiving the transplant were 30% and 64% in the BMT group and 5% and 91% in the PBSCT group (P <.03). Overall survival 1000 days after receiving the transplant was 66% after BMT and 94% after PBSCT (P <.02). In the multivariate analysis, only acute GVHD significantly influenced TRM (P <.01).

Immune Status of Infants Fed Soy‐Based Formulas With or Without Added Nucleotides for 1 Year: Part 2: Immune Cell Populations

ABSTRACTBackgroundInfants fed a soy protein isolate–based formula have immunization responses similar to breast‐fed infants. However, cellular aspects of the immunologic development of soy‐fed infants have not been studied extensively. Nucleotides added to milk‐based formula benefit infant immune status, but reports of the immunologic effects of adding nucleotides to soy‐based formula are not available. This study examines immune cell populations of infants fed soy protein isolate formulas with and without added nucleotides for 1 year.MethodsNewborn, term infants studied in a masked 12‐month feeding trial were assigned randomly to soy formula groups with and without added nucleotides (n = 94, n = 92). A nonrandomized human milk/formula‐fed cohort (n = 81), was concurrently enrolled. Blood samples were collected at 6, 7, and 12 months. Thirty‐two immune cell populations were characterized using three‐color flow cytometry. Cellular markers were chosen to assess general pediatric immune status, emphasizing maturation and activation of B, T, and NK lymphocytes.ResultsAll cell populations, number and percentages, were within age‐related normal ranges. The only significant difference found between soy formula and human milk/formula‐fed infants was the percentage of CD57+ NK T cells at 12 months (human milk/formula &gt; soy formula, P = 0.034). There were significant differences at some time points between human milk/formula‐fed and nucleotide‐supplemented soy formula–fed infants in populations of lymphocytes, eosinophils, total T, helper T, naive helper, memory/effector helper, CD57−T, and CD11b+CD8+NK cells. None of the cell populations differed between infants fed soy formula versus soy plus nucleotides.ConclusionsInfants fed this commercial soy formula demonstrated immune cell status similar to human milk/formula‐fed infants, consistent with normal immune system development. The addition of nucleotides to soy formula did not significantly change specific individual immune cell populations but tended to increase numbers and percentages of T cells and decreased numbers and percentages of NK cells.

CORD BLOOD LYMPHOCYTE FUNCTIONS IN NEWBORNS FROM A REMOTE MARITIME POPULATION EXPOSED TO ORGANOCHLORINES AND METHYLMERCURY

The consumption of fish and sea mammals can be an important source of exposure to organochlorine compounds (OCs) and heavy metals in populations relying on seafood for subsistence. Exposure to these substances, especially during the prenatal period, has been shown to induce immunotoxic effects in mammals. Immunological status was assessed in 48 newborns from a remote maritime population living on the Lower and Mid North Shore of the St. Lawrence River (subsistence fishing group) and 60 newborns from the coastal urban center of Sept-Îles (reference group). Women were recruited upon arrival at Sept-Îles regional hospital to give birth. Cord blood samples were collected for organochlorine and heavy metal analyses and to isolate lymphocytes for immunological assays (proportions and functional responses of the main cellular subsets T, B, and NK (natural killer) cells. Concentrations of polychlorinated biphenyls (PCBs) and mercury were respectively three-and twofold higher, significantly greater, in the subsistence fishing group than in the reference group. Compared to the reference group, the subsistence fishing group showed significant decreases in the proportion of the naive helper T-cell subset CD4 + CD45RA + , T-cell proliferation following an in vitro mitogenic stimulation, and plasma immunoglobulin M (IgM) level, while plasma IgG level was increased. NK cytolytic activities were similar in both groups. The proportion of CD4 + CD45RA + cells was inversely correlated to mercury and PCBs, while T-cell clonal expansion was negatively associated with PCBs and p,p '-DDE. Mercury was inversely correlated to plasma IgM. Data show that subtle functional alterations of the developing human immune system may result from in utero exposure to OCs and mercury. Epidemiological studies are needed to determine the relevance of these alterations in predicting detrimental health effects in the developing child.

Thrombangitis obliterans: Subpopulationen der Leukozyten und zirkulierende Immunkomplexe

Background: The etiology of thrombangitis obliterans is still unclear. Although cellular infiltration of the vessel wall is known, no studies on peripheral blood mononuclear cells are reported. Therefore, we assessed leucocyte subpopulations and circulating immune complexes in patients with thrombangitis obliterans and a control group of normal people. Patients and methods: 31 patients (40 ± 2 years, 24 male, 7 female) with thrombangitis obliterans were included, based on the following criteria: age of manifestation, acral ischemia in legs and arms, previous thrombophlebitis or phlebitis saltans. Manifestation of atherosclerosis or other vasculitic manifestations were excluded. Leucocyte subpopulations, levels of C-reactive protein (CRP) and circulating immune complexes (CIC) were investigated. An age-matched control group (n = 25) was recruited from voluntary blood donors. Results: Leucocyte counts in the thrombangitis group (mean ± SD: 10839 ± 782/nl) were significantly different from the control group (6205 ± 414/nl, p &lt; 0.0001). The same was true for absolute counts of granulocytes, monocytes and lymphocytes. The results were independent from CRP, which was elevated only in 6 patients. Relative counts of naive helper T-cells were significantly lower in the patient group. HLA-DR expression on B-cells was lower on the patients’ lymphocytes. The concentrations of IgA, IgG and IgM in CIC were higher in the thrombangitis patients compared to the control group. C1q-binding capacity and phosphatidylserine antibodies showed no differences. Conclusions: Patients suffering from thrombangitis obliterans show alterations of leucocyte counts and their subpopulations as well as alterations of the humoral (IgCIC) immune system.