Psoriasis Severity, Health-Related Quality of Life, Work Productivity, and Activity Impairments Among Patients With Moderate to Severe Psoriasis Receiving Systemic Treatment: Real-World Data From Clinical Practice in Spain.

BACKGROUND AND OBJECTIVE: The treatment of psoriasis should not only focus on skin affectations but also weigh the parameters for health-related quality of life (HRQoL), thereby tackling the concept of cumulative life course impairment (CLCI) and treating the patient from a holistic perspective. The CRYSTAL study aimed to characterize psoriasis with real-word data from Spanish clinical practice in patients with moderate to severe disease who received continuous systemic treatment for at least 24 weeks by using the absolute Psoriasis Area and Severity Index (PASI) score and its correlation to HRQoL. MATERIAL AND METHODS: This was a non-interventional, cross-sectional study conducted in 30 centers in Spain, with 301 patients between the ages of 18 and 75 years. The study collected data regarding current treatment and absolute PASI and their relationship to HRQoL using the Dermatology Life Quality Index (DLQI), to activity impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire, and to treatment satisfaction. RESULTS: The mean (SD) age was 50.5 (12.5) years, with a duration of disease of 14 (14.1) years. The mean (SD) absolute PASI reported was 2.3 (3.5), with 28.7% of patients presenting with PASI from >1 to ≤3 and 22.6% with PASI>3. Higher PASI scores were associated with higher DLQI (p<0.001) and WPAI scores and lower levels of treatment satisfaction (p<0.001). CONCLUSIONS: These data indicate that achieving lower absolute PASI values may correlate not only with better HRQoL but also with better work productivity and treatment satisfaction.

Psoriasis Severity, Health-Related Quality of Life, Work Productivity, and Activity Impairments Among Patients With Moderate to Severe Psoriasis Receiving Systemic Treatment: Real-World Data From Clinical Practice in Spain. / [Artículo traducido] Gravedad de la psoriasis, calidad de vida relacionada con la salud, productividad laboral y deterioro de la actividad en pacientes con psoriasis moderada a grave que reciben tratamiento sistémico: datos de la vida real de la práctica clínica en España.

BACKGROUND AND OBJECTIVE: The treatment of psoriasis should not only focus on skin affectations but also weigh the parameters for health-related quality of life (HRQoL), thereby tackling the concept of cumulative life course impairment (CLCI) and treating the patient from a holistic perspective. The CRYSTAL study aimed to characterize psoriasis with real-word data from Spanish clinical practice in patients with moderate to severe disease who received continuous systemic treatment for at least 24 weeks by using the absolute Psoriasis Area and Severity Index (PASI) score and its correlation to HRQoL. MATERIAL AND METHODS: This was a non-interventional, cross-sectional study conducted in 30 centers in Spain, with 301 patients between the ages of 18 and 75 years. The study collected data regarding current treatment and absolute PASI and their relationship to HRQoL using the Dermatology Life Quality Index (DLQI), to activity impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire, and to treatment satisfaction. RESULTS: The mean (SD) age was 50.5 (12.5) years, with a duration of disease of 14 (14.1) years. The mean (SD) absolute PASI reported was 2.3 (3.5), with 28.7% of patients presenting with PASI from >1 to ≤3 and 22.6% with PASI>3. Higher PASI scores were associated with higher DLQI (p<0.001) and WPAI scores and lower levels of treatment satisfaction (p<0.001). CONCLUSIONS: These data indicate that achieving lower absolute PASI values may correlate not only with better HRQoL but also with better work productivity and treatment satisfaction.

Different proteomic strategies to identify genuine Small Ubiquitin-like MOdifier targets and their modification sites in Trypanosoma brucei procyclic forms.

SUMOylation is an important post-translational modification conserved in eukaryotic organisms. In Trypanosoma brucei, SUMO (Small Ubiquitin-like MOdifier) is essential in procyclic and bloodstream forms. Furthermore, SUMO has been linked to the antigenic variation process, as a highly SUMOylated focus was recently identified within chromatin-associated proteins of the active variant surface glycoprotein expression site. We aimed to establish a reliable strategy to identify SUMO conjugates in T. brucei. We expressed various tagged variants of SUMO from the endogenous locus. His-HA-TbSUMO was useful to validate the tag functionality but SUMO conjugates were not enriched enough over contaminants after affinity purification. A Lys-deficient SUMO version, created to reduce contaminants by Lys-C digestion, was able to overcome this issue but did not allow mapping many SUMOylation sites. This cell line was in turn useful to demonstrate that polySUMO chains are not essential for parasite viability. Finally, a His-HA-TbSUMO(T106K) version allowed the purification of SUMO conjugates and, after digestion with Lys-C, the enrichment for diGly-Lys peptides using specific antibodies. This site-specific proteomic strategy led us to identify 45 SUMOylated proteins and 53 acceptor sites unambiguously. SUMOylated proteins belong mainly to nuclear processes, such as DNA replication and repair, transcription, rRNA biogenesis and chromatin remodelling, among others.

Cysteinyl leukotriene receptor (CysLT) antagonists decrease pentylenetetrazol-induced seizures and blood-brain barrier dysfunction.

Current evidence suggests that inflammation plays a role in the pathophysiology of seizures. In line with this view, selected pro-inflammatory arachidonic acid derivatives have been reported to facilitate seizures. Kainate-induced seizures are accompanied by leukotriene formation, and are reduced by inhibitors of LOX/COX pathway. Moreover, LTD4 receptor blockade and LTD4 synthesis inhibition suppress pentylenetetrazol (PTZ)-induced kindling and pilocarpine-induced recurrent seizures. Although there is convincing evidence supporting that blood-brain-barrier (BBB) dysfunction facilitates seizures, no study has investigated whether the anticonvulsant effect of montelukast is associated with its ability to maintain BBB integrity. In this study we investigated whether montelukast and other CysLT receptor antagonists decrease PTZ-induced seizures, as well as whether these antagonists preserve BBB during PTZ-induced seizures. Adult male albino Swiss mice were stereotaxically implanted with a cannula into the right lateral ventricle, and two electrodes were placed over the parietal cortex along with a ground lead positioned over the nasal sinus for electroencephalography (EEG) recording. The effects of montelukast (0.03 or 0.3 µmol/1 µL, i.c.v.), pranlukast (1 or 3 µmol/1 µL, i.c.v.), Bay u-9773 (0.3, 3 or 30 nmol/1 µL, i.c.v.), in the presence or absence of the agonist LTD4 (0.2, 2, 6 or 20 pmol/1 µL, i.c.v.), on PTZ (1.8 µmol/2 µL)-induced seizures and BBB permeability disruption were determined. The animals were injected with the antagonists, agonist or vehicle 30 min before PTZ, and monitored for additional 30 min for the appearance of seizures by electrographic and behavioral methods. BBB permeability was assessed by sodium fluorescein method and by confocal microscopy for CD45 and IgG immunoreactivity. Bay-u9973 (3 and 30 nmol), montelukast (0.03 and 0.3 µmol) and pranlukast (1 and 3 µmol), increased the latency to generalized seizures and decreased the mean amplitude of EEG recordings during seizures. LTD4 (0.2 and 2 pmol) reverted the anticonvulsant effect of montelukast (0.3 µmol). Montelukast (0.03 and 0.3 µmol) prevented PTZ-induced BBB disruption, an effect that was reversed by LTD4 at the dose of 6 pmol, but not at the doses 0.2 and 2 pmol. Moreover, the doses of LTD4 (0.2 and 2 pmol) that reverted the effect of montelukast on seizures did not alter montelukast-induced protection of BBB, dissociating BBB protection and anticonvulsant activity. Confocal microscopy analysis revealed that 1. PTZ increased the number of CD45+ and double-immunofluorescence staining for CD45 and IgG cells in the cerebral cortex, indicating BBB leakage with leukocyte infiltration; 2. while LTD4 (6 pmol) potentiated, montelukast decreased the effect of PTZ on leukocyte migration and BBB, assessed by double-immunofluorescence staining for CD45 and IgG cells in the cannulated hemisphere. Our data do not allow us ruling out that mechanisms unrelated and related to BBB protection may co-exist, resulting in decreased seizure susceptibility by montelukast. Notwithstanding, they suggest that CysLT1 receptors may be a suitable target for anticonvulsant development.

Phenotypic and functional changes on phagocytic cells recruited at the site of Candida albicans infection after chronic varied stress exposure.

The transition of Candida albicans from commensalism to pathogenicity is associated with the immune status of the host; resistance to fungus involves macrophages (Mphi) and polymorphonuclear neutrophils (PMN), which act as effector cells. T-cell function is also involved. Previously, we found that in Wistar rats exposed to chronic varied stress (CVS) immediately after C. albicans infection (Ca-S group) some functions of phagocytic cells, such as killer activity and NO production, were strongly modified compared with unstressed, infected animals (Ca group). We examined the phenotypic and functional changes of these effector cells recruited at the site of C. albicans infection. The recruitment of peritoneal cells (PC) was markedly reduced in Ca-S animals and the arrival of Mphi and PMN was selectively diminished after CVS exposure. The integrin CD11b/CD18, implicated in migration and C. albicans phagocytosis, was downregulated in Mphi of Ca-S animals. The activation markers CD54 and MHC-II were upregulated in Mphi after fungal contact. The expression of CD54 was only changed in Ca-S rats. Finally, TNF-alpha production was reduced in PC of Ca-S animals, suggesting an impairment of functional activity. Taken together, the phenotypic and functional changes detected in effector cells may account for the decreased resistance to candidiasis seen in conjunction with CVS. The changes seen also expand our knowledge of the role of Mphi in the control of C. albicans dissemination.

Identification of a CD8alpha(+) dendritic cell subpopulation in rat spleen and evaluation of its OX-62 expression.

Rat spleen DC and bone marrow-derived DC were isolated and characterized by morphology and flow cytometry. We found a CD8alpha(+) DC subpopulation representing 19-48% (27.4 +/- 12.0) of total spleen DC. The OX-62 expression on total spleen DC was 41-59% (51.8 +/- 7.5). Myeloid bone marrow-derived DC were negative for CD8alpha and OX-62. We demonstrated the coexpression of CD8alpha and OX-62 molecules, at least in a portion CD8alpha(+) spleen DC. Both CD8alpha(+) and CD8alpha(-) spleen DC subpopulations separated by MACS were able to induce an in vivo primary immune response to OVA. The immune response induced by the CD8alpha(-) DC subpopulation was higher (P < 0.05). We identified a CD8alpha(+) DC subpopulation in rat spleen less effective in inducing an immune response than CD8alpha(-) DC. Moreover, our results suggest the presence of DC subpopulations with different lineages in DC preparations based on OX-62 expression.

Mechanisms for induction of immunosuppression during experimental cryptococcosis: role of glucuronoxylomannan.

In previous work we have demonstrated that spleen mononuclear (Spm) cells from rats obtained 14 days after infection with Cryptococcus neoformans showed a diminution in proliferative response to Concanavalin A (Con A). In this study we further investigate some characteristics of the Spm cell population involved in the immunosuppressor phenomenon induced by C. neoformans. We observed that unstimulated Spm cells expressing T-cell receptor (TCR+) from infected rats were reduced in number after 96 h of culture. When the Spm cells from infected rats were stimulated with Con A, increased production of IL-10, reduced levels of IL-2, and decreased CD11a surface expression were shown. These immunosuppressor phenomena were also observed when the capsular polysaccharide, glucuronoxylomannan (GXM), was added to cultures of Spm cells from normal rats. However, GXM had a more pronounced effect in reducing the number of cells surviving in culture than that observed during infection and produced an increase in IL-4 production by Con-A-stimulated Spm cells. Addition of anti-IL-10 monoclonal antibody to cultures restored the lymphoproliferation of Spm cells from infected animals, indicating that IL-10 production is a suppressor mechanism of cell-mediated immunity during experimental infection. The results presented here indicate that at least two mechanisms mediate the nonspecific suppression in this model of cryptococcosis: IL-10 production and diminution of the number of T cells. GXM could be involved, since it has a pronounced effect in the reduction of Spm cells in vitro.

[Induction of primary immune response by rat dendritic cells]. / Inducción de respuesta inmune primaria por células dendríticas de rata.

In this work we generated dendritic cells (DC) from rat bone marrow cultures stimulated with GM-CSF and IL-4. After 10 days of culture, we obtained numerous mature DC showing morphological characteristics of DC and high levels of MHC class II molecules. Also, we isolated DC from rat spleen on the bases of their differential adherence and low-density properties. The purity of these cells was > 90% according to morphology and MHC class II expression. To evaluate the capacity of bone marrow DC, immature spleen DC or spleen DC cultured 24h with GM-CSF (mature spleen DC), to elicit an immune response to ovalbumin (OVA), DC were loaded with this antigen and transferred to normal rats. Both bone marrow and spleen DC induced delayed type hypersensitivity responses (DTH). However, mature DC from spleen induced a stronger immune response against OVA with the highest DTH values (p < 0.05). These differences in the induction of the immune response correlated with higher expression of MHC class II molecules on mature DC.

Inducción de respuesta inmune primaria por células dendríticas de rata. / [Induction of primary immune response by rat dendritic cells]

In this work we generated dendritic cells (DC) from rat bone marrow cultures stimulated with GM-CSF and IL-4. After 10 days of culture, we obtained numerous mature DC showing morphological characteristics of DC and high levels of MHC class II molecules. Also, we isolated DC from rat spleen on the bases of their differential adherence and low-density properties. The purity of these cells was > 90

according to morphology and MHC class II expression. To evaluate the capacity of bone marrow DC, immature spleen DC or spleen DC cultured 24h with GM-CSF (mature spleen DC), to elicit an immune response to ovalbumin (OVA), DC were loaded with this antigen and transferred to normal rats. Both bone marrow and spleen DC induced delayed type hypersensitivity responses (DTH). However, mature DC from spleen induced a stronger immune response against OVA with the highest DTH values (p < 0.05). These differences in the induction of the immune response correlated with higher expression of MHC class II molecules on mature DC.

Inflammatory arthritic process, iridocyclitis and immune response to articular and ocular antigens in Wistar rats injected with T. gondii trophozoites.

The present study deals with the potential role of T. gondii in inducing an arthritic inflammatory process. Wistar rats were injected subcutaneously (sc) into the right footpad with viable T. gondii trophozoites emulsified in incomplete Freund's adjuvant (IFA). The control group was injected with IFA. All parasite-injected animals developed a local inflammatory process characterized by hind limb swelling and marked restriction of ankle motility approximately 25 days after injection. Histopathogical studies of the joints, carried out 90 days after injection, revealed intense mononuclear infiltration, proliferation of granulation tissue, giant cells and necrosis in the synovia of 90% of T. gondii-injected rats. Strikingly, 40% (4/10) of the parasite-injected animals developed iridocyclitis, which was characterized by intense mononuclear infiltration around the iris-ciliary microvasculature in two animals and a slightly pronounced infiltrate of polymorphonuclear and mononuclear cells in two other animals. Antibodies to soluble T. gondii antigens (STAg) were detected in all parasite-injected rats. Antibodies against articular and ocular antigens such as proteoglycans, type II collagen, retinal S antigen and iris antigens were detected by ELISA in 40, 80, 70 and 70% of T. gondii -injected animals, respectively. Control animals injected with IFA failed to develop any articular or ocular process or humoral immune response. The present study demonstrated that footpad sc injection of Wistar rats with viable T. gondii trophozoites was able to induce a localized inflammatory arthritic process which, in some of the animals, was accompanied by iridocyclitis and immune response against articular and ocular components.

Granulocyte-macrophage colony-stimulating factor protects dendritic cells from liposome-encapsulated dichloromethylene diphosphonate-induced apoptosis through a Bcl-2-mediated pathway.

Liposome-encapsulated dichloromethylene diphosphonate (L-MDP) has been used for depleting cells of the monocyte-macrophage lineage. We have undertaken this study to investigate whether dendritic cells are susceptible to this liposome-encapsulated compound. Dendritic cells were cultured in the presence of L-MDP and further processed for apoptosis detection. The highly characteristic DNA cleavage into oligonucleosome-sized fragments, incorporation of biotinylated dUTP into DNA strand breaks and the typical ultrastructural features of apoptosis were evident in dendritic cells exposed to the drug. More importantly, we demonstrated that granulocyte-macrophage colony-stimulating factor protects dendritic cells not only from apoptosis induced by the exogenous compound but also from spontaneous apoptosis. Western blot analysis revealed that this protection was tightly correlated with the activation of a Bcl-2-mediated pathway. Regulation of the apoptotic threshold of dendritic cells will be advantageous for the generation of new insights in immunotherapy.

[The factors related to eating behaviors in a juvenile urban population]. / Factores relacionados con los comportamientos alimentarios en una población juvenil urbana.

OBJECTIVE: To find certain personal and social factors relating to the attitudes to food and the nutritional habits of young people. DESIGN: Observational, crossover study with randomised distribution. SETTING: Txantrea, a quarter of Pamplona with 20,578 inhabitants and with 1739 14 to 19-year olds in school. PARTICIPANTS: Sample of 465 people between 14 and 19, randomised and stratified for age. RESULTS: Under the life-style heading, 69% (64.3-73) tried to eat a varied diet; 56% (51.3-60.5) took part in the choice of family meals; and 52% (47, 3-56.3) ate snacks. On personal questions, 67% (62.3-71.1) said they had quite a lot or a lot of interest in diet; 50% (45.3-54.5) said they were quite concerned or very concerned about their diet; 22% (18.3-25.9) thought themselves obese or slightly obese, whereas 8% (5.7-10.9) were in fact obese. 71% (66.7-74.9) were satisfied with their physique. 28% (24.1-32.2) had been on a diet. 81% (76.7-84.6) thought that young people gave a lot or quite a lot of importance to their physique. 78% (73.9-81.4) thought that the communication media had a lot or quite a lot of influence on the life-styles of young people. On education and information, 33% (28.7-37.3) thought they were well-informed on dietary questions, basically by the family. 38% (33.5-42.3) thought they were good or very good at cooking. 58% (53.3-62.3) said they were available for training in nutrition. The people with more interest in nutritional questions were more concerned and better informed. Being female was associated with: more interest and concern, having followed a diet, the view that the media had a big influence, feeling pressured by the family to eat more and availability for education. Being male was associated with: satisfaction with their physique, and thinking they were very thin, thin or balanced. CONCLUSIONS: Critical attitudes to the influence of the media were seen. There was a lot of concern about, and interest, in, nutrition. There was also quite a lot of not very healthy behaviour.

Induction of autoimmune prostatitis using liposomes is associated to peritoneal cells activation.

PROBLEM: Study and characterization of rat peritoneal cells (PC) involved in the induction of autoimmune prostatitis after the intraperitoneal administration of native extract of accessory glands (RAG) associated with liposomes (RAGL). METHOD OF STUDY: Induction of the autoimmune response in normal recipients by transferring PC or adherent-PC loaded with RAGL (RAGL-PC), but not with PC loaded with empty liposomes (L-PC). Characterization of the morphology, the ultrastructure, and the phenotype of L-PC or RAGL-PC. Study of the respiratory burst by the nitroblue tetrazolium (NBT) reduction assay after stimulation with phorbol myristate acetate (PMA) in both L-PC and RAGL-PC. RESULTS: Liposomes attached to the cell surface of the M phi were observed by electron microscopy. FACS analyses showed a similar staining pattern with high expression of Ia molecules on L-PC and RAGL-PC compared with controls. PMA-stimulated L-PC or RAGL-PC markedly reduced the NBT compared with controls. CONCLUSION: Our results suggest that the effective uptake of liposomes and the initial activation of PC together with a prolonged stimulatory effect help to disrupt the tolerance state. The present experimental model is an interesting approach to further characterize events associated with antigenic presentation when an autoimmune response is triggered.

Involvement of peritoneal dendritic cells in the induction of autoimmune prostatitis.

We have been working within a model of autoimmune prostatitis induced by the intraperitoneal administration of saline extract of rat male accessory glands (RAG) associated to liposomes. The intraperitoneal administration of RAG-liposomes elicits both primary and secondary cellular autoimmune responses to RAG as well as organ-specific lesions. To evaluate the participation of dendritic cells (DC) in the induction of the autoimmune response, we purified peritoneal DC (PDC) after a single injection of RAG-liposomes and we characterized this population by morphology and phenotype. Based on adherence and morphologic criteria, we determined that PDC comprised approximately 1% of the total peritoneal cells. The ultrastructure of the dendritic cell enriched fraction was assessed by electron microscopy. By FACS analysis, PDC showed a two to three-fold increase in expression of the IA molecule compared to macrophages. They expressed low but positive levels of the CD14 marker, and intermediate levels of both CD11b (Mac-1) and CD54 (ICAM-1) adhesion molecules. In addition, PDC transferred either intravenously or intraperitoneally efficiently elicited the autoimmune response to RAG in normal receptors. These results support the involvement of peritoneal dendritic cells in the induction of autoimmune prostatitis, modifying the idea of macrophages as the single antigen presenting cell in the peritoneal cavity.

Mast cells in accessory glands of experimentally induced prostatitis in male Wistar rats.

We studied the histological modifications in the accessory glands of autoimmune rats. Adult male Wistar rats were id immunized three times with saline extract of rat male accessory glands (RAG) chemically modified (MRAG) in complete Freund's adjuvant (CFA) (groups 1, 2, and 3). Prior to the first immunization with MRAG-CFA groups 2 and 3 received peritoneal cells obtained from rats that had been injected 2 or 24 hr previously with low doses of RAG. Furthermore, an additional group (group 4) ip immunized with liposome-associated-RAG was incorporated. The delayed-type hypersensitivity response studied 10 or 15 days after first immunization was positive for rats of groups 1, 3, and 4, while it was negative for rats of group 2. Serum samples obtained on Day 45 and studied by ELISA showed high levels of autoantibodies in groups 1 and 2 and lower levels of autoantibodies in group 3, but did not show autoantibodies in group 4. The histological studies performed 10 days after the last immunization showed organ-specific lesions in the accessory glands in animals of groups 1, 3, and 4. Infiltration of mononuclear cells was the main alteration in group 1, while infiltration of mast cells and polymorphonuclear leukocytes were present in specimens of groups 3 and 4. The main finding of this study was a significant increase (P < 0.0005) in the extent of mast cell degranulation in the specimens of accessory glands stained with toluidine blue. Our results suggest that mast cells are activated in our experimental model of autoimmune disease.

Cells involved in the regulation of the autoimmune response to rat male accessory glands.

1. The immunization of Wistar rats with 5 mg of chemically modified rat male accessory glands saline extract (MRAG) incorporated into complete Freund's adjuvant (CFA) induced a delayed type hypersensitivity (DTH) response to rat male accessory glands (RAG). Pretreatment with peritoneal cells (PC) obtained from rats 2 h after an intraperitoneal (ip) injection of a partially purified fraction (FI) of RAG (FI-PC2h) suppressed the DTH response to MRAG after immunization with MRAG-CFA, while pretreatment with PC obtained 24 h after an ip injection of FI-RAG (FI-PC24h) induced potentiation of the DTH response to MRAG. 2. The injection of spleen mononuclear cells (SpM), obtained from rats rendered unresponsive to MRAG by pretreatment with FI-PC2h, into normal syngeneic recipients markedly prevented the DTH reaction to MRAG. The transfer of SpM cells from animals injected with FI-PC24h (potentiated animals) to suppressed recipients (recipients of FI-PC2h on days -10 and -3, prior to immunization with MRAG-CFA) showed that SpM cells did not eliminate the suppression state in these recipients, but when they were transferred to normal recipients, they were able to induce a positive response to RAG (P < 0.005). 3. The study of the phenotypic characteristics of the SpM cells prior to transfer showed similar numbers of CD4 and IL-2R SpM cells in both potentiated and normal animals. However, the number of CD8 cells was significantly reduced in SpM cells from potentiated animals compared to that observed in SpM cells from normal animals (P < 0.05).

Cells involved in the regulation of the autoimmune response to rat male accessory glands

1. The immunization of Wistar rats with 5 mg of chemically modified rat male accessory glands saline extract (MRAG) incorporated into complete Freund's adjuvant (CFA) induced a delayed type hypersensitivity (DTH) response to rate male accessory glands (RAG). Pretreatment with peritoneal cells (PC) obtained from rats 2 h after an intraperitoneal (ip) injection of a partially purified fraction (FI) of RAG (FI-PC2h) suppressed the DTH response to MRAG after immunization with MRAG-CFA, while pretreatment with PC obtained 24 h after an ip injection of FI-RAG (FI-PC24h) induced potentiation of the DTH response to MRAG. 2. The injection of spleen mononuclear cells (SpM), obtained from rats rendered unresponsive to MRAG by pretreatment with FI-PC2h, into normal syngeneic recipients markedly prevented the DTH reaction to MRAG. The transfer of SpM cells from animals injected with FI-PC24h (potentiated animals) to suppressed recipients (recipients of FI-PC2h on days -10 and -3, prior to immunization with MRAG-CFA) showed that SpM cells did not eliminate the suppression state in these recipients, but when they were transferred to normal recipients, they were able to induce a positive response to RAG (P<0.005). 3. The study of the phenotypic characteristics of the SpM cells prior to transfer showed similar numbers of CD4 and IL-2R SpM cells in both potentiated and normal animals. However, the number of CD8 cells was significantly reduced in SpM cells from potentiated animals compared to that observed in SpM cells from normal animals (P<0.05)

Characterization of an immunoregulatory cell subset involved in the up-regulation of the autoimmune response to rat male accessory glands.

PROBLEM: We studied the regulation of the autoimmune response to rat male accessory glands (RAG) using liposomes as adjuvants. METHOD: Adult male Wistar rats were submitted to three intraperitoneal (i.p.) immunizations with 750 micrograms of saline extract of RAG associated with liposomes. The delayed type hypersensitivity (DTH) response studied approximately 10 days after each immunization developed after the first immunization, having a remission state after the second one and a clear increase after the third injection. In a further study, spleen mononuclear (SpM) cells obtained form immunized rats 10 days after the third immunization (DTH positive) or from normal rats were separated as adherent (VV+) or nonadherent (VV-) to Vicia villosa population. In VV+ SpM cells from immunized or normal animals an enhanced percentage of OX8+ cells (P < .05 and P < .01, respectively) was found, but in VV- SpM cells from the same groups of rats an enhanced percentage of W3/25+ cells (P < .01 and P < .05, respectively) was found when they were studied by immunofluorescence. Later on, we transferred total VV+ or VV- SpM cells from i.p. immunized rats to immunized recipients 10 days after the second immunization (DTH negative). The DTH response was enhanced in recipients of total or VV+ SpM cells (P < .01). It was also observed that the transfer of VV- SpM cells from immunized rats or total or VV+ SpM cells from normal rats did not reduce the suppression state observed after the second injection (P = NS). The total SpM cells obtained 10 days after the third immunization (DTH positive) were able to transfer autoimmune response to RAG to normal animals (P < .01), whereas VV+ SpM cells did not show that capacity (P = NS).