An immunomodulatory function for neutrophils during the induction of a CD4+ Th2 response in BALB/c mice infected with Leishmania major.

The possible immunomodulatory role of polymorphonuclear leukocytes (PMN) in CD4+ T lymphocyte differentiation in mice was examined by studying the effect of transient depletion of PMN during the early phase after Leishmania major delivery. A single injection of the PMN-depleting NIMP-R14 mAb 6 h before infection with L. major prevented the early burst of IL-4 mRNA transcription otherwise occurring in the draining lymph node of susceptible BALB/c mice. Since this early burst of IL-4 mRNA transcripts had previously been shown to instruct Th2 differentiation in mice from this strain, we examined the effect of PMN depletion on Th subset differentiation at later time points after infection. The transient depletion of PMN in BALB/c mice was sufficient to inhibit Th2 cell development otherwise occurring after L. major infection. Decreased Th2 responses were paralleled with partial resolution of the footpad lesions induced by L. major. Furthermore, draining lymph node-derived CD4+ T cells from PMN-depleted mice remained responsive to IL-12 after L. major infection, unlike those of infected BALB/c mice receiving control Ab. PMN depletion had no effect when the NIMP-R14 mAb was injected 24 h postinfection. The protective effect of PMN depletion was shown to be IL-12 dependent, as concomitant neutralization of IL-12 reversed the protective effect of PMN depletion. These results suggest a role for an early wave of PMN in the development of the Th2 response characteristic of mice susceptible to infection with L. major.

NY-ESO-1-specific circulating CD4+ T cells in ovarian cancer patients are prevalently T(H)1 type cells undetectable in the CD25+ FOXP3+ Treg compartment.

Spontaneous CD4(+) T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4(+) T cells in EOC patients with spontaneous immune responses to the antigen are prevalently T(H)1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer(+) cells ex vivo, at an average frequency of 1:25,000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer(+) cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25(+)FOXP3(+)Treg. Thus, spontaneous CD4(+) T-cell responses to ESO in cancer patients are prevalently of T(H)1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines.

CD4+CD25+Foxp3+ regulatory T cells: from basic research to potential therapeutic use.

Regulatory T cells control immune responses to self- and foreign-antigens and play a major role in maintaining the balance between immunity and tolerance. This article reviews recent key developments in the field of CD4+CD25+Foxp3+ regulatory T (TREG) cells. It presents their characteristics and describes their range of activity and mechanisms of action. Some models of diseases triggered by the imbalance between TREG cells and effector pathogenic T cells are described and their potential therapeutic applications in humans are outlined.

A decrease of plasma macrophage migration inhibitory factor concentration is associated with lower numbers of circulating lymphocytes in experimental Plasmodium falciparum malaria.

Macrophage migration inhibitory factor (MIF) has recently been implicated in the pathogenesis of malarial anaemia. However, field studies have reported contradictory results on circulating MIF concentrations in patients with clinically overt Plasmodium falciparum malaria. We determined plasma MIF levels over time in 10 healthy volunteers during experimental P. falciparum infection. Under fully controlled conditions, MIF levels decreased significantly during early blood-stage infection and reached a nadir at day 8 post-infection. A decrease in the number of circulating lymphocytes, which are an important source of MIF production, paralleled the decrease in MIF levels. Monocyte/macrophage counts remained unchanged. At MIF nadir, the anti-inflammatory cytokine interleukin (IL)-10, which is an inhibitor of T-cell MIF production, was detectable in only 2 of 10 volunteers. Plasma concentrations of the pro-inflammatory cytokines IL-8 and IL-1beta were only marginally elevated. We conclude that circulating MIF levels decrease early in blood-stage malaria as a result of the decline in circulating lymphocytes.

Between Immunology And Tolerance: Controlling Immune Responses Employing Tolerogenic Dendritic Cells

Dendritic cells (DCs) are the most efficient antigen presenting cells, they provide co-stimulation, are able to secrete various proinflammatory cytokines and therefore play a pivotal role in shaping adaptive immune responses. Moreover, they are important for the promotion and maintenance of central and peripheral tolerance through several mechanisms like the induction of anergy or apoptosis in effector T cells or by promoting regulatory T cells. The murine CD8α+ (MuTu) dendritic cell line was previously derived and described in our laboratory. The MuTu cell line has been shown to maintain phenotypical and functional characteristics of endogenous CD8α+ DCs. They are able to cross-present exogenous antigens to CD8+ T cells and produce interleukin (IL-) 12 upon engagement of Toll like receptors. The cell line constitutes an infinite source of homogenous, phenotypically well-defined dendritic cells. This allows us to investigate the role and potential of specific molecules in the induction as well as regulation of immune responses by DCs in a rational and standardized way. In a first project the MuTu dendritic cell line was transduced in order to stably express the immunosuppressive molecules IL-10, IL-35 or the active form of TGF-β (termed IL-10+DC, IL-35+DC or actTGFβ+DC). We investigated the capability of these potentially suppressive or tolerogenic dendritic cell lines to induce immune tolerance and explore the mechanisms behind tolerance induction. The expression of TGF-β by the DC line did not affect the phenotype of the DCs itself. In contrast, IL-10+ and IL-35+DCs were found to exhibit lower expression of co-stimulatory molecules and MHC class I and II, as well as reduced secretion of pro-inflammatory cytokines upon activation. In vitro co-culture with IL-35+, IL10+ or active TGFβ+ DCs interfered with function and proliferation of CD4+ and CD8+ T cells. Furthermore, IL-35 and active TGF-β expressing DC lines induced regulatory phenotype on CD4+ T cells in vitro without or with expression of Foxp3, respectively. In different murine cancer models, vaccination with IL-35 or active TGF-β expressing DCs resulted in faster tumor growth. Interestingly, accelerated tumor growth could be observed when IL-35-expressing DCs were injected into T cell-deficient RAG-/- mice. IL-10expressing DCs however, were found to rather delay tumor growth. Besides the mentioned autocrine effects of IL-35 expression on the DC line itself, we surprisingly observed that the expression of IL-35 or the addition of IL-35 containing medium enhances neutrophil survival and induces proliferation of endothelial cells. Our findings indicate that the cytokine IL-35 might not only be a potent regulator of adaptive immune responses, but it also implies IL-35 to mediate diverse effects on an array of cellular targets. This abilities make IL-35 a promising target molecule not only for the treatment of auto-inflammatory disease but also to improve anti-cancer immunotherapies. Indeed, by applying active TGFβ+ in murine autoimmune encephalitis we were able to completely inhibit the development of the disease, whereas IL-35+DCs reduced disease incidence and severity. Furthermore, the preventive transfer of IL-35+DCs delayed rejection of transplanted skin to the same extend as the combination of IL-10/actTGF-β expressing DCs. Thus, the expression of a single tolerogenic molecule can be sufficient to interfere with the adequate activation and function of dendritic cells and of co-cultured T lymphocytes. The respective mechanisms of tolerance induction seem to be different for each of the investigated molecule. The application of a combination of multiple tolerogenic molecules might therefore evoke synergistic effects in order to overcome (auto-) immunity. In a second project we tried to improve the immunogenicity of dendritic cell-based cancer vaccines using two different approaches. First, the C57BL/6 derived MuTu dendritic cell line was genetically modified in order to express the MHC class I molecule H-2Kd. We hypothesized that the expression of BALB/c specific MHC class I haplotype (H-2Kd) should allow the priming of tumor-specific CD8+ T cells by the otherwise allogeneic dendritic cells. At the same time, the transfer of these H-2Kd+ DCs into BALB/c mice was thought to evoke a strong inflammatory environment that might act as an "adjuvant", helping to overcome tumor induced immune suppression. Using this so called "semi-allogeneic" vaccination approach, we could demonstrate that the delivery of tumor lysate pulsed H-2Kd+ DCs significantly delayed tumor growth when compared to autologous or allogeneic vaccination. However, we were not able to coherently elucidate the cellular mechanisms underlying the observed effect. Second, we generated MuTu DC lines which stably express the pro-inflammatory cytokines IL-2, IL-12 or IL-15. We investigated whether the combination of DC vaccination and local delivery of pro-inflammatory cytokines might enhance tumor specific T cell responses. Indeed, we observed an enhanced T cell proliferation and activation when they were cocultured in vitro with IL-12 or IL-2-expressing DCs. But unfortunately we could not observe a beneficial or even synergistic impact on tumor development when cytokine delivery was combined with semi-allogeneic DC vaccination.

Role of Th1 and Th2 cells in autoimmune demyelinating disease

Evidence is accumulating that Th1 cells play an important role in the development of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), whereas Th2 cells contribute to recovery from disease. A major determinant in the development of Th1 and Th2 cells is the type of antigen-presenting cell (APC) involved and its functional characteristics, e.g., the production of interleukin-12. Therefore, modulation of APC might interfere with the development of Th1 type responses and as such be beneficial for MS and EAE. The potential of cytokines, in particular interleukin-10, and glucocorticoids to exert a selective effect on APC, and as a consequence to affect the Th1-Th2 balance in EAE, is discussed

Cytokines as determinants of disease and disease interactions

The immune response to pathogens results in both host resistance and immunopathology. Cytokines and in particular those lymphokines produced by Th1 and Th2 cells play a key role in determining the balance between these two immunologic outcomes. Recent data suggest that interleukin-10, a product of both Th2 cells and macrophages, protects the host against excessive immunopathology. The cytokine environment generated by different pathogens may also influence the course and outcome of infections with unrelated organisms. This relationship may be particularly important in the case of HIV-1 where prior Th1 or Th2 biases established by helminth or intracellular infections may influence either initial viral susceptibility or drive progression to AIDS through immune activation

Cytokines in innate and acquired immunity to Trypanosoma cruzi infection

Resistance to Trypanosoma cruzi infections is critically dependent on cytokine-mediated activation of cell-mediated immune effector mechanisms. This review focuses on the role of IL-10, TNF-<FONT FACE="Symbol">a</font>, IFN-<FONT FACE="Symbol">g</font> and IL-12 in controlling T. cruzi replication by the innate and specific immune systems of the vertebrate host. A study performed on mice with disrupted recombinase-activating genes (RAG/KO), which lack T and B lymphocytes, revealed the importance of IL-12, IFN-<FONT FACE="Symbol">g</font> and TNF-<FONT FACE="Symbol">a</font> in the resistance against T. cruzi mediated by the innate immune system. In addition, data from experiments using IL-10 KO, RAG/KO and double RAG/IL-10 KO mice indicating an in vivo regulatory role of IL-10 in innate and T. cruzi-specific immunity are discussed

Development of a Glycocluster Adjuvant Mimicking Natural Yeast beta-(1,2)-Structures

Allergy is characterized by T helper (Th) 2-type immune response after encounter with an allergen leading to subsequent immunoglobulin (Ig) E-mediated hypersensitivity reaction and further allergic inflammation. Allergen-specific immunotherapy (SIT) balances the Th2-biased immunity towards Th1 and T regulatory responses. Adjuvants are used in allergen preparations to intensify and modify SIT. ��-(1,2)-oligomannoside constituents present in Candida albicans (C. albicans) cell wall possess Th1-type immunostimulatory properties. The aim of this thesis was to develop a ��-(1,2)-linked carbohydrate compound with known structure and anti-allergic properties to be applied as an adjuvant in SIT. First the immunostimulatory properties of various fungal extracts were studied. C. albicans appeared to be the most promising Th1-inducing extract, which led to the synthesis of various mono- or divalent oligomannosides designed on the basis of C. albicans. These carbohydrates did not induce strong cytokine production in human peripheral blood mononuclear cell (PBMC) cultures. In contrast to earlier reports using native oligosaccharides from C. albicans, synthetic ���-(1,2)-linked mannotetraose did not induce any tumor necrosis factor production in murine macrophages. Next, similarities with synthesized divalent mannosides and the antigenic epitopes of ��-(1,2)-linked C. albicans mannan were investigated. Two divalent compounds inhibited specific IgG antibodies binding to below 3 kDa hydrolyzed mannan down to the level of 30���50% showing similar antigenicity to C. albicans. Immunomodulatory properties of synthesized carbohydrate assemblies ranging from mono- to pentavalent were evaluated. A trivalent acetylated dimannose (TADM) induced interleukin-10 (IL-10) and interferon-�� responses. TADM also suppressed birch pollen induced IL-4 and IL-5 responses in allergen (Bet v) stimulated PBMCs of birch pollen allergic subjects. This suppression was stronger with TADM than with other used adjuvants, immunostimulatory oligonucleotides and monophosphoryl lipid A. In a murine model of asthma, the allergen induced inflammatory responses could also be suppressed by TADM on cytokine and antibody levels.

Ischemic post-conditioning attenuates the intestinal injury induced by limb ischemia/reperfusion in rats

The purpose of this study was to investigate the protective effects of ischemic post-conditioning on damage to the barrier function of the small intestine caused by limb ischemia-reperfusion injury. Male Wistar rats were randomly divided into 3 groups (N = 36 each): sham operated (group S), lower limb ischemia-reperfusion (group LIR), and post-conditioning (group PC). Each group was divided into subgroups (N = 6) according to reperfusion time: immediate (0 h; T1), 1 h (T2), 3 h (T3), 6 h (T4), 12 h (T5), and 24 h (T6). In the PC group, 3 cycles of reperfusion followed by ischemia (each lasting 30 s) were applied immediately. At all reperfusion times (T1-T6), diamine oxidase (DAO), superoxide dismutase (SOD), and myeloperoxidase (MPO) activity, malondialdehyde (MDA) intestinal tissue concentrations, plasma endotoxin concentrations, and serum DAO, tumor necrosis factor-&#945; (TNF-&#945;), and interleukin-10 (IL-10) concentrations were measured in sacrificed rats. Chiu&#8217;s pathology scores for small intestinal mucosa were determined under a light microscope and showed that damage to the small intestinal mucosa was lower in group PC than in group LIR. In group PC, tissue DAO and SOD concentrations at T2 to T6, and IL-10 concentrations at T2 to T5 were higher than in group LIR (P < 0.05); however, tissue MPO and MDA concentrations, and serum DAO and plasma endotoxin concentrations at T2 to T6, as well as TNF-&#945; at T2 and T4 decreased significantly (P < 0.05). These results show that ischemic post-conditioning attenuated the permeability of the small intestines after limb ischemia-reperfusion injury. The protective mechanism of ischemic post-conditioning may be related to inhibition of oxygen free radicals and inflammatory cytokines that cause organ damage.

Plasma cytokine response, lipid peroxidation and NF-&#954;B activation in skeletal muscle following maximum progressive swimming

Our objective was to determine lipid peroxidation and nuclear factor-&#954;B (NF-&#954;B) activation in skeletal muscle and the plasma cytokine profile following maximum progressive swimming. Adult male Swiss mice (N = 15) adapted to the aquatic environment were randomly divided into three groups: immediately after exercise (EX1), 3 h after exercise (EX2) and control. Animals from the exercising groups swam until exhaustion, with an initial workload of 2% of body mass attached to the tail. Control mice did not perform any exercise but were kept immersed in water for 20 min. Maximum swimming led to reactive oxygen species (ROS) generation in skeletal muscle, as indicated by increased thiobarbituric acid reactive species (TBARS) levels (4062.67 &#177;1487.10 vs 19,072.48 &#177; 8738.16 nmol malondialdehyde (MDA)/mg protein, control vs EX1). Exercise also promoted NF-&#954;B activation in soleus muscle. Cytokine secretion following exercise was marked by increased plasma interleukin-6 (IL-6) levels 3 h post-exercise (P < 0.05). Interleukin-10 (IL-10) levels were reduced following exercise and remained reduced 3 h post-exercise (P < 0.05). Plasma levels of other cytokines investigated, monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-&#945;), interferon-gamma (IFN-&#947;) and interleukin-12 (IL-12), were not altered by exercise. The present findings showed that maximum swimming, as well as other exercise models, led to lipid peroxidation and NF-&#954;B activation in skeletal muscle and increased plasma IL-6 levels. The plasma cytokine response was also marked by reduced IL-10 levels. These results were attributed to exercise type and intensity.

Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

Inflammation induced by increased frequency of intermittent hypoxia is attenuated by tempol administration

The levels of serum inflammatory cytokines and the activation of nuclear factor kappa B (NF-&#954;B) and hypoxia inducible factor-1&#945; (HIF-1&#945;) in heart tissues in response to different frequencies of intermittent hypoxia (IH) and the antioxidant tempol were evaluated. Wistar rats (64 males, 200-220 g) were randomly divided into 6 experimental groups and 2 control groups. Four groups were exposed to IH 10, 20, 30, or 40 times/h. The other 2 experimental groups were challenged with IH (30 times/h) plus tempol, either beginning on day 0 (IH30T0) or on day 29 (IH30T29). After 6 weeks of challenge, serum levels of tumor necrosis factor (TNF)-&#945;, intracellular adhesion molecule (ICAM)-1, and interleukin-10 were measured, and western blot analysis was used to detect NF-&#954;B p65 and HIF-1&#945; in myocardial tissues. Serum levels of TNF-&#945; and ICAM-1 and myocardial expression of NF-&#954;B p65 and HIF-1&#945; were all significantly higher in IH rats than in controls (P<0.001). Increased IH frequency resulted in more significant changes. Administration of tempol in IH rats significantly reduced levels of TNF-&#945;, ICAM-1, NF-&#954;B and HIF-1&#945; compared with the non-tempol-treated group (F=16.936, P<0.001). IH induced an inflammatory response in a frequency-dependent manner. Additionally, HIF-1&#945; and NF-&#954;B were increased following IH administration. Importantly, tempol treatment attenuated this effect.

R��gulation des chaperons de la pr��sentation antig��nique par ubiquitination

La cha��ne invariante forme un complexe nonam��rique avec les mol��cules classiques du CMH de classe II. HLA-DM et HLA-DO, des mol��cules non-classiques de classe II, sont aussi impliqu��es dans la pr��sentation des peptides antig��niques aux lymphocytes T. Ces mol��cules chaperones de la pr��sentation antig��nique modulent la capacit�� d���une cellule �� pr��senter des antig��nes par les molo��cules classiques du CMH de classe II. La r��gulation transcriptionnelle des mol��cules chaperones, tout comme celle des autres mol��cules du CMH de classe II, est assur��e par le transactivateur CIITA. La mol��cule HLA-DR peut ��tre r��gul��e n��gativement de mani��re post-traductionnelle par ubiquitination gr��ce �� l���enzyme E3 ubiquitine ligase MARCH1. Celle-ci est induite par l���interleukine-10 dans les monocytes. L���objectif de ce projet ��tait de d��terminer si l���ubiquitination par MARCH1 peut aussi r��guler l���expression des mol��cules chaperones de la pr��sentation antig��nique. Les exp��riences furent r��alis��es dans le contexte de co-transfections en cellules HEK293T. L���expression des mol��cules fut ��valu��e par immunomarquages et cytom��trie de flux. Il a ��t�� montr�� que l���isoforme p33 de la cha��ne invariante est r��gul�� n��gativement en pr��sence de MARCH1 �� partir de la surface cellulaire, causant ainsi sa d��gradation. Tel que d��montr�� par l���utilisation d���un mutant d��pourvu de queue cytoplasmique, cette derni��re r��gion n���est pas indispensable �� ce ph��nom��ne. Une hypoth��se est qu���une mol��cule non-identifi��e, associ��e �� Ii, serait ubiquitin��e par MARCH1, l���entra��nant dans sa r��gulation n��gative. Il fut d��terminer que cette mol��cule n�����tait pas CXCR2, un r��cepteur pouvant ��tre impliqu��, avec la cha��ne invariante et CD44, en tant que r��cepteur de MIF (Macrophage Inhibitory Factor). Il fut aussi montr�� que HLA-DO peut ��tre cibl�� par MARCH1 mais ceci ne semble pas ��tre un ph��nom��ne dominant; l���expression des complexes DO/DM n�����tant pas affect��e bien qu���ils entrent en interaction avec MARCH1. L���expression de HLA-DM n���est pas affect��e par MARCH1. Il n���a toutefois pas ��t�� d��termin�� hors de tout doute si MARCH1 peut modifier DM; des r��sultats obtenus avec une queue cytoplasmique de DM poss��dant une lysine laissant sugg��rer qu���il est possible que MARCH1 interagisse avec DM. Dans l���ensemble, les travaux d��montrent que l���ubiquitination par MARCH1 joue un r��le dans la r��gulation post-transcriptionnelle de la cha��ne invariante p33 mais pas HLA-DO et HLA-DM.

��tude du r��le de l'interleukine-32 dans l'infection �� VIH-1

Les progresseurs lents du VIH-1 sont de rares sujets asymptomatiques pendant plusieurs ann��es sans th��rapie antir��trovirale. Parmi ces sujets �� progression lente vers le SIDA, il est possible qu���un sous-groupe perde le contr��le de leur infection apr��s plusieurs ann��es de contr��le. Notre laboratoire a analys�� l���expression diff��rentielle de diff��rentes prot��ines et voies mol��culaires associ��es �� la perte de contr��le de l���infection: l���interleukine-32 (IL-32) est une cytokine pro-inflammatoire dont le niveau des isoformes alpha et delta a significativement diminu�� chez les progresseurs lents lors de la perte de contr��le. Par ailleurs, des ��tudes ant��rieures ont attribu��, de fa��on intrigante, �� l���IL-32 aussi bien des propri��t��s anti-VIH-1 que des propri��t��s immunosuppressives induisant un environnement propice �� la r��plication du VIH-1. Ce projet de maitrise s���est pench�� sur l���implication de l���IL-32 dans la progression de l���infection �� VIH-1 avec un accent particulier sur les progresseurs lents. Nous avons principalement mesur�� les niveaux d���IL-32 des sujets s��ropositifs comparativement aux sujets VIH n��gatif et estim�� les fonctions de cette cytokine �� travers des ��tudes longitudinales et de corr��lation. Nous avons observ�� que l���IL-32 total demeure plus ��lev�� chez les s��ropositifs comparativement aux sujets VIH n��gatif. ��galement, l���infection par le VIH-1 entraine une augmentation du niveau d���IL-32 total. De plus, apr��s une ann��e de th��rapie antir��trovirale, les taux plasmatiques d���IL-32 total demeurent significativement plus ��lev��s que ceux des sujets VIH n��gatif. Comme attendu, le taux d���IL-32 total augmente lors de la perte de contr��le de l���infection chez les progresseurs lents. Une forte concentration plasmatique d���IL-32 total co��ncide avec: 1) une augmentation du taux plasmatique de sCD14 et de la cytokine pro-inflammatoire IL-6, 2) une baisse du compte cellulaire CD4 et une augmentation de la charge virale. Un taux plasmatique ��lev�� de CCL5 pourrait pr��dire une faible concentration d���IL-32 total. L���isoforme alpha de l���IL-32 est plus ��lev��e dans le plasma des sujets VIH n��gatif tandis que l���IL-32 gamma semble induire un environnement pro-inflammatoire et immunosuppressif. Il ressort �� l���issue de ces observations que l���augmentation de l���IL-32 total est associ��e �� la progression de l���infection �� VIH-1 et pourrait constituer un biomarqueur permettant d���appr��cier le pronostic de cette infection.