Depletion of peritoneal CD5+ B cells has no effect on the course of Leishmania major infection in susceptible and resistant mice.

The mouse peritoneal cavity contains a unique self-renewing population of B cells (B-1) derived from fetal liver precursors and mainly producing polyreactive antibodies. Since B-1 cells are a potential source of IL-10, it has been suggested that these cells may contribute to the susceptibility of BALB/c mice to Leishmania major infection by skewing the T helper cell network towards a Th2 phenotype. Accordingly, L. major infection of B cell-defective BALB/c Xid mice (lacking B-1 cells) induces less severe disease compared with controls. However, in addition to the lack of B-1 cells, the Xid immune deficiency is characterized by high endogenous interferon-gamma (IFN-gamma) production. In the present study, the role of B-1 cells during L. major infection was investigated in mice experimentally depleted of peritoneal B-1 cells. Six weeks old C57Bl/6 and BALB/c mice were lethally irradiated and reconstituted with autologous bone marrow which allows systemic depletion of B-1 cells. Untreated BALB/c, C57Bl/6 as well as BALB/c Xid mice were used as controls. After reconstitution, mice were injected with L. major amastigotes and progression was followed using clinical, parasitological and immunological criteria. As previously reported, BALB/c Xid mice showed a significant reduction in disease progression. In contrast, despite the dramatic reduction of B-1 cells, B-1-depleted BALB/c mice showed similar or even worse disease progression compared with control BALB/c mice. No differences were found between B-1-depleted or control C57Bl/6 mice. Our data suggest that the B-1 cells do not contribute to the susceptibility of BALB/c mice to L. major infection.     

Macrophages and protective immunity in Mycobacterium lepraemurium infections in a ''resistant'' (C57Bl) and a ''susceptible'' (BALB/c) mouse strain

The progressive low resistance form of M. lepraemurium infection in BALB/c mice and the more benign form of infection in C57Bl mice provided appropriate models for analysing the role of macrophages in the spectrum of leprosy in man. Although C57Bl mice were more resistant to both primary and challenge infections than BALB/c mice, peritoneal macrophages from infected mice of both strains were bacteriostatic in vitro. However, a diffusion chamber technique demonstrated that macrophages of BALB/c mice were usually less effective in controlling mycobacterial multiplication in vivo than those of C57Bl mice. This technique also revealed two diffusible factors in infected mice of both strains: one able to activate, the other able to suppress macrophage anti-mycobacterial activity. In C57Bl mice, the macrophage activating factor was apparently dominant; in BALB/c mice, the macrophage suppressor factor seemed to play the major role.     

Experimental African trypanosomiasis: differences in cytokine and nitric oxide production by macrophages from resistant and susceptible mice.

Immunosuppression in experimental infections with Trypanosoma congolense is mediated by the synergistic action of macrophages and a novel lymphocyte(s), which involves the activity of IFN-gamma as well as IL-10. BALB/c mice are highly susceptible while C57Bl/6 mice are relatively resistant to T. congolense infections. Plasma and/or supernatants of spleen cell cultures of infected susceptible BALB/c mice have more IL-10 but less IL-12 than those of infected relatively resistant C57Bl/6 mice. Cells of a BALB/c macrophage cell line, when pulsed with T. congolense, produce more IL-10 and IL-6, but have less TNF-alpha mRNA, than equally treated cells of a C57Bl/6 cell line. Peritoneal and/or bone marrow-derived macrophages obtained from BALB/c mice, pulsed with T. congolense in culture, produce less nitric oxide, TNF-alpha and IL-12, but more IL-6 and IL-10 than equally treated macrophages isolated from C57Bl/6 mice. We suggest that genetic resistance to African trypanosomiasis is expressed at the level of the macrophage.     

BALB/c and C57Bl/6 mice infected with virulentBurkholderia pseudomalleiprovide contrasting animal models for the acute and chronic forms of human melioidosis

Burkholderia pseudomalleiis the aetiological agent of melioidosis, a life-threatening bacterial disease occurring in many species of animals, including man. Infection in humans commonly manifests as one of three clinical presentations: acute, subacute or chronic disease. Investigations were undertaken to assess the suitability of BALB/c and C57Bl/6 mice as animal models for the different forms of human melioidosis. The course of infection in BALB/c mice was similar to that which occurs in acute human infection. By contrast, infection of C57Bl/6 mice appeared to mimic chronic human melioidosis. While BALB/c mice suffered a rapidly-progressive bacteraemia which resulted in host death by 96 h, C57Bl/6 mice were able to prevent this, and typically remained asymptomatic for up to 6 weeks. LD₅₀values of 4 cells and 2.5×10⁴cells for BALB/c and C57Bl/6 mice, respectively, reflect these observations. The heightened level of resistance toB. pseudomalleiobserved in C57Bl/6 mice was suggested to have a genetic basis, when the susceptibilities of first filial and reciprocal backcross generations were examined. Growth kinetics ofB. pseudomalleiwithin BALB/c and C57Bl/6 peritoneal exudate cell (PEC) cultures were examined to investigate PEC microbicidal efficiency as a determinant of host susceptibility. C57Bl/6 PEC cultures exhibited greater microbicidal efficiency towardsB. pseudomalleiwhen compared to BALB/c cells, indicating that susceptibility may be determined by non-specific, cellular mechanisms. Collectively, these results suggest that the BALB/c and C57Bl/6 strains of mice may provide excellent models for acute and chronic human melioidosis, respectively.     

Quantitative and qualitative differences in bronchoalveolar inflammatory cells in Pseudomonas aeruginosa-resistant and -susceptible mice

The difference in severity of Pseudomonas aeruginosa-induced chronic lung infection may be determined by differences in host inflammatory responses. In the present study we investigate this possibility using BALB/c and C57Bl/6 mice, resistant and susceptible, respectively, to chronic lung infection with P. aeruginosa. Following intratracheal inoculation of P. aeruginosa-impregnated agar beads, C57Bl/6 mice mounted a stronger inflammatory response with significantly higher total cell numbers in the bronchoalveolar lavage fluid compared with BALB/c mice. While polymorphonuclear leucocytes were the predominant cell in C57Bl/6 mice, macrophages constituted the majority in BALB/c mice at day 7 post-infection. Alveolar macrophages from C57Bl/6 mice showed significantly higher spontaneous production of nitric oxide (NO) at day 7 post-infection compared with BALB/c mice. Following in vitro stimulation with heat-killed Pseudomonas antigen, these cells produced significantly higher NO compared with cells from BALB/c mice at day 21 post-infection. Production of tumour necrosis factor-alpha (TNF-α) by alveolar macrophages was significantly higher at day 7 in BALB/c mice compared with C57Bl/6 mice, which showed significantly higher levels at day 28 post-infection. Taken together, these results suggest that defects in the host inflammatory process contribute to the variable outcome of chronic lung infection with P. aeruginosa. An exaggerated inflammatory response dominated by polymorphonuclear cells correlates with susceptibility to infection, whilst a modest inflammatory response dominated by macrophages correlates with resistance. Moreover, the quantity and timing of production of NO and TNF-α by alveolar macrophages may modulate the course and outcome of infection.     

Induction of soluble antitumoral mediators by synthetic analogues of bacterial lipoprotein in bone marrow-derived macrophages from LPS-responder and -nonresponder mice

Macrophage-dependent antitumoral activity is partly mediated by soluble factors including cytokines, reactive-oxygen intermediates (ROIs), and reactive-nitrogen intermediates (RNIs). Activation of macrophages for tumor cytotoxicity can be achieved with various bacterial compounds, such as lipopolysaccharides (LPSs), muramyl-dipeptides, and lipopeptides. We studied the production and release of oxygen radicals, nitric oxide, and tumor necrosis factor alpha (TNF-alpha) by bone marrow-derived macrophages (BMDMs) of different mouse inbred strains after they were stimulated with the lipopeptide P3CSK4, a water-soluble synthetic analogue of the lipidated N terminus of bacterial lipoprotein. The lipopeptide was able to induce a strong, long lasting release of oxygen radicals in BALB/c mouse macrophages. Furthermore, it induced nitric oxide release from BMDMs of several mouse strains (BALB/c, C57Bl/6, C57Bl/10ScSn, Sv129, NMRI, and LPS-nonresponder C57Bl/10ScCr). Stimulation with P3CSK4 also resulted in comparable production of TNF-alpha in LPS-responder and nonresponder BMDMs from C57Bl/10ScSn mice and C57Bl/10ScCr mice, respectively. All three antitumoral mediators reached functional levels or concentrations as shown by the strong cytostatic/cytotoxic activity of lipopeptide-activated macrophages for the cell lines Abelson 8-1, M12.5/P815, and L929, which are sensitive to ROIs, nitric oxide, and TNF-alpha, respectively. We found that synthetic lipopeptides can induce the secretion of effective levels of soluble tumor-cytotoxic/cytostatic mediators in BMDMs of LPS-responsive and, of particular interest, also of LPS-unresponsive mice. This result could indicate that the highly effective bacterial-macrophage activators P3CSK4 and LPS use different receptors and/or different intracellular signal transduction pathways.     

Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice

Brucella abortus is an intracellular bacterial pathogen that causes chronic infections in humans and a number of agriculturally important species of animals. It has been shown that BALB/c mice are more susceptible to infections with virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In experiments described here, gene knock-out mice were utilized to elucidate some of the salient components of resistance. Resistant C57BL/6 mice with gene deletions or disruptions in the interferon-γ (IFN-γ), perforin or β₂-microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the first week after infection. However, only the IFN-γ knock-out mice had a sustained inability to control infections and this resulted in death of the mice at approximately 6 weeks post-infection. These mice had a continual increase in the number of bacterial colony-forming units (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN-γ gene were infected they had more splenic CFU at one week post-infection than control mice but the increase was not statistically significant and by 3 weeks they did not have more CFU than control mice. Moreover, the number of splenic bacteria did not increase in the BALB/c IFN-γ knock-out mice between 6 and 10·5 weeks, although they died at 10·5 weeks, the time by which normal BALB/c mice were clearing the infection. Death in both strains of IFN-γ gene disrupted mice coincided with symptoms of cachexia and macrophages comprised ≥75% of the splenic leucocytes.     

Differences in migration inhibitory factor production by C57Bl/6 and BALB/c mice in allergic and irritant contact dermatitis

Two strains of mice, BALB/c and C57Bl/6, which are known to differ in their inflammatory responsiveness to allergens, were analyzed regarding their expression of macrophage migration inhibitory factor (MIF). Allergic contact dermatitis to 2,4-dinitro-1-fluorobenzene and irritant contact dermatitis to croton oil were studied immunohistologically at designated time intervals after elicitation. BALB/c mice presented a significantly more intense ear swelling response than C57Bl/6 mice and showed a strong endothelial MIF expression in the early phase of inflammation in both allergic and irritant contact dermatitis. Endothelial MIF expression was much weaker in C57Bl/6 mice. Furthermore, the infiltration rate of inflammatory cells (MIF+ and BM8+ macrophages, Lyt2+ and L3T4+ T cells) was significantly higher in BALB/c than in C57Bl/6 mice. We conclude that genetically determined differences of susceptibility to allergens and irritants in BALB/c and C57Bl/6 mice are reflected by the intensity of MIF expression in the microvascular endothelium and immigrating inflammatory cells. MIF seems to appear as first molecular equivalent of developing inflammation and probably determines the degree of cellular infiltration.     

Genetic differentiation of poly I:C from B:9-23 peptide induced experimental autoimmune diabetes

Type 1 diabetes is an immune-mediated disease, in which T cells of the adaptive immune system mediate beta cell destruction. Recently the innate immune system has been linked to etiopathogenesis of several autoimmune diseases including type 1 diabetes, as innate effector cells (e.g. dendritic cells, monocytes/macrophages and NK cells) can prime and promote or regulate (auto)immune responses. We have previously developed an experimental autoimmune diabetes (EAD) model with insulin peptide B:9-23 immunization in transgenic H-2(d)mice expressing the costimulatory molecule B7.1 in their islets (under the Rat Insulin Promotor, RIP). We compared the induction of diabetes with polyinosinic-polycytidylic acid (Poly I:C), a mimic of double stranded viral RNA versus insulin B:9-23 peptide in mice following backcrossing of the B7.1 transgene on to BALB/c mice from original B7.1 C57Bl/6 mice. We find that diabetes induction by Poly I:C is C57Bl/6 associated, whereas B:9-23 peptide induced diabetes and induction of insulin autoantibodies (IAA) are dependent on BALB/c genes. This B:9-23 peptide induced diabetes is consistent with MHC class II H-2(d)being necessary for the response to this peptide. Of note Poly I:C induction of diabetes was lost while B:9-23 induction was retained with backcrossing to BALB/c mice. Interaction of genes and environment (antigenic epitope and viral mimic) can be important in the pathogenesis of immune mediated diabetes and activation of the innate immune system (e.g. Poly I:C) may be one key determinant.     

Tryptophan hydroxylase 2 genotype determines brain serotonin synthesis but not tissue content in C57Bl/6 and BALB/c congenic mice

Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in the synthesis of brain serotonin (5-HT). In a previous report, a single nucleotide polymorphism in mTph2 (C1473G) reduced 5-HT synthesis by 55%. Mouse strains expressing the 1473C allele, such as C57Bl/6, have higher 5-HT synthesis rates than strains expressing the 1473G allele, such as BALB/c. Many studies have attributed strain differences to Tph2 genotype without ruling out the potential role of alterations in other genes. To test the role of the C1473G polymorphism in strain differences, we generated C57Bl/6 and BALB/c mice congenic for the Tph2 locus. We found that the 1473G allele reduced 5-HT synthesis in C57Bl/6 mice but had no effect on 5-HT tissue content except for a slight reduction (15%) in the frontal cortex. In BALB/c mice, the 1473C allele increased 5-HT synthesis but again did not affect 5-HT tissue content. At the same time, 5-hydroxyindoleacetic acid (5-HIAA) was significantly elevated in BALB/c congenic mice. In C57Bl/6 mice, there was no effect of genotype on 5-HIAA levels. BALB/c mice had lower expression of monoamine oxidase A and B than C57Bl/6 mice, but there was no effect of Tph2 genotype. On the tail suspension test, escitalopram treatment reduced immobility regardless of genotype. These data demonstrate that the C1473G polymorphism determines differences in 5-HT synthesis rates among strains but only minimally affects 5-HT tissue levels.     

Immunity Parameters in Mice of Different Strains

Quantitative composition and functional activity of immunocompetent cells differ in mice of different strains. The counts of T cells in the bone marrow and spleen, proliferative activity of T cells in the spleen, levels of IL-2 and IL-10 production by splenic T cells, number of antigen-specific T cells and their functional activity are low in C57Bl/6, BALB/c, and CC57W mice and high in CBA/CaLac, DBA/2, and C3H animals. Low phagocytic activity of peritoneal macrophages was detected in BALB/c and CC57W mice and high activity in C3H animals. The content of antibody-producing cells in the spleens of C57Bl/6, BALB/c, and CC57W mice is higher than in CBA/CaLac, DBA/2, C3H, A/SN, and AKR/JY mice. Functional activity of B cells is lower in BALB/c and CC57W compared to CBA/CaLac and DBA/2 mice. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 8, pp. 189–191, August, 2005     

Immune reactions in different mouse strains

The responses of immunocompetent cells to thymus-dependent antigen differ in mice of different strains. Immunization stimulated phagocytic activity of peritoneal macrophages in CBA/CaLac, DBA/2, and BALB/c mice and suppressed it in CC57W mice. By the formation of antibody-producing cells in the spleen in response to thymus-dependent antigen DBA/2 and CBA/CaLac mice can be classified as high responders, BALB/c mice as medium-responders, and C57Bl/6 and CC57W mice as low responders.     

Resistance and susceptibility of mice to bacterial infection. IV. Functional specificity in natural resistance to facultative intracellular bacteria

The effect of opsonic antibody on resistance of susceptibility of three strains of mice, C57Bl/10, BALB/c, and CBA to the intracellular bacteria Listeria monocytogenes, Salmonella typhimurium, and Brucella abortus was tested. Bacteria were opsonized by serum treatment before their injection into mice, or the mice were preimmunized by injection with alcohol killed bacteria which induces antibody without macrophage activation. Antibody did not increase the rate of clearance of Listeria from the bloodstream, nor did it affect the subsequent growth of that organism in the spleen and liver. Blood clearance of S. typhimurium and of B. abortus was increased by preopsonization with specific antibody, indicating that opsonins were a limiting factor in resistance to these two bacteria. However, neither opsonization before infection nor immunization with alcohol killed vaccines had any effect on the strain distribution of resistance/susceptibility, which differs for each of the three intracellular pathogens. Thus, even in the presence of adequate opsonization the three strains of mice showed different patterns of resistance/susceptibility to Listeria, S. typhimurium, and B. abortus. This implies that each has a unique cellular mechanism of early nonspecific resistance.     

Characterization of anti-acetylcholine receptor (AChR) antibodies from mice differing in susceptibility for experimental autoimmune myasthenia gravis (EAMG).

In the murine model for EAMG we investigated the relation between disease susceptibility and fine specificity of anti-AChR antibodies obtained from high susceptible C57Bl/6 and low susceptible BALB/c mice after immunization with Torpedo acetylcholine receptor (tAChR). Anti-AChR MoAbs with fine specificity for the main immunogenic region (MIR), the alpha-bungarotoxin (alpha-BT)/acetylcholine binding sites and other extra- and intracellular epitopes were isolated from both mouse strains. In total, nine out of 38 MoAbs obtained from C57Bl/6 mice were directed against extracellular epitopes on mouse AChR in contrast to only one out of 27 MoAbs from BALB/c mice. A difference in antibody repertoire may underlie the difference in pathogenic response observed between these mouse strains. These results indicate that strain-specific differences in disease susceptibility in murine EAMG may be related to differences in the available repertoire of potential pathogenic antibodies.     

Regulation of the immune response in experimental models of autoimmune disorders: resistance of (NZB X NZW)F1 mice to tolerance induction in vivo

Studies were carried out to test whether tolerance to alloantigens and to heterologous proteins could be induced in (NZB X NZW)F1 (B/W) female mice, compared with females of various other mouse strains, including BALB/c, C3H/eb, C57Bl/Ka and (BALB/c X C57Bl/6)F1. Untreated BALB/c and B/W mice were resistant to tolerance induction by deaggregated BSA, while all other strains were susceptible, as indicated by their lack of response to antigen challenge. Tolerance induction to BSA was further potentiated in all mouse strains including BALB/c with the exception of B/W, following prior conditioning of the mice with total lymphoid irradiation (TLI). Similarly, specific and permanent tolerance to H-2 incompatible alloantigens was successfully induced in TLI conditioned BALB/c, C3H/eb, (BALB/c X C57Bl/6)F1 injected with bone marrow cells, however, B/W mice were resistant. Stable chimeras could be established in TLI treated B/W mice only across a semi-allogeneic combination (BALB/c--greater than B/W). No graft vs host disease (GVHD) was observed in any of the chimeras including B/W mice. We conclude that B/W mice are resistant to tolerance induction to heterologous proteins and alloantigens, even after TLI conditioning. We postulate that this phenomenon is a function of both the intrinsic properties of the haemopoietic stem cells, including their differentiated progeny, as well as characteristics of their cellular microenvironment.     

Morphofunctional changes of BALB/c and C57BL/6 mice's immune system under chronic bacterial gram-negative endotoxicosis

Chronic endotoxicosis was modeled by subcutaneous injection of the sepharose in complex with LPS. In these conditions we have studied morphofunctional changes of the immune system of BALB/c and C57Bl/6 mice, which are characterized by the different types of the immune response (Th2 type is predominant in BALB/c, Th1--in C57Bl/6). In the 1st-7th day t in the serum of BALB/c mice the endotoxin level increased in 21.3 times, in C57Bl/6--in 20.6 times. The endotoxin antibodies significantly decreased in 1th-7th days, on the 14th day it increased in the serum of both mice's strains. Morphofunctional changes of the immune system after chronic endotoxicosis were different in BALB/c and C57BI/6 mice. On the 1th day after injection of LPS and sepharose, in the thymus of C57Bl/6 mice the cortex layer was exhausted because of cell death, in the thymus of BALB/c mice II-III stages of accidental involution were developed. On the 7-14th day after injection of LPS and sepharose in the spleen of C57Bl/6 mice T- and B-zones were hyperplastic, however in spleen of BALB/c mice only T-zone were enlarged. After LPS and sepharose injection changes of cytokine production synthesized by KonA activated splenic cells were found out. In both strains the level of proinflammatory cytokines--TNFalpha and IL-1beta decreased, as well the Th1-cytokine IL-2. The production o fTh2-cytokine - IL-4, significantly decreased only in C57BI/6 mice. We suggest that damaging effect of LPS injection is determined by predominant Th2 or Th2 types of the immune response.     

Effect of cyclophosphamide treatment on the course of Mycobacterium lepraemurium infection and development of delayed-type hypersensitivity reactions in C57B1 and BALB/c mice.

Pre-treatment of Mycobacterium lepraemurium susceptible, BALB/c, and resistant, C57Bl, mice with cyclophosphamide markedly altered the development of delayed hypersensitivity during footpad infections with this organism. A tuberculin-type response demonstrated by untreated C57Bl mice was significantly intensified after week 3 in cyclophosphamide-pre-treated mice although this response had returned to normal levels by week 8. A Jones-Mote-type response demonstrated throughout experiments by untreated BALB/c mice was considerably increased in magnitude by week 3 in cyclophosphamide-pre-treated mice. By week 6 this response had become considerably protracted and was of the tuberculin-type. By week 8 however this response had started to diminish and by week 12 cyclophosphamide-treated and untreated BALB/c mice produced similar Jones-Mote-type responses when skin-tested. Cyclophosphamide pre-treatment had no effect on the growth of M. lepraemurium in C57Bl mice over 12 weeks. In BALB/c mice however cyclophosphamide-pre-treated mice demonstrated considerable resistance to infection at weeks 8 and 10 after infection but not thereafter. Whereas the magnitude of the delayed hypersensitivity response in C57Bl mice could not be correlated with resistance such a relationship could be demonstrated in BALB/c mice.     

Experimental cutaneous leishmaniasis: transmission electron microscopy of the inoculation site

Tissue response against inoculation of Leishmania (Leishmania) amazonensis promastigotes in the hind footpad was quite different between two strains of mice: in BALB/c animals there was parasitism of perineurial cells by the 8th week post inoculation (WPI) and heavy parasitism of macrophages, as well as degenerated extracellular parasites close to collagen fibers at the 39th WPI, whereas in C57Bl/6j mice there was heavy parasitism of macrophages at 6th WPI, dermal vessels with high endothelial cell at 21st WPI and well preserved intracellular amastigote forms by 51st WPI. In both animals there was no parasitism of keratinocytes or Langerhans cells. Thus BALB/c mice were useful as an experimental model for diffuse cutaneous leishmaniasis and showing a new feature, parasitism of perineurial cells, whereas C57Bl/6j animals show hypersensitivity signs, together with a few preserved parasites, only late in the course of infection. From a morphological point of view, there were no differences in macrophages, or in the interaction between this target cell and the parasite, between the animal models studied. This suggests that the difference in the response of the hosts towards the parasite could depend on the way in which they activate a cellular, i.e. lymphocyte mediated immune, response.     

Lack of a role for natural killer cells in early control of Brucella abortus 2308 infections in mice.

Studies were conducted to determine if natural killer (NK) cells are important for early control of the virulent strain Brucella abortus 2308 following infection of mice with high or low challenge doses. Splenocytes from C57BL/10 and BALB/c mice that had been infected with the lower dose of B. abortus displayed increased cytotoxicity against YAC-1 cells during the first week after infection, while infection of C57BL/10 mice with the higher challenge dose either did not alter the level of NK cytotoxic activity or decreased it, depending upon the time postinfection. In vivo depletion of NK cells by monoclonal antibody anti-NK1.1 or polyclonal anti-asialoGM1 antiserum did not result in an increase in the number of brucellae recovered from the spleens or livers of the brucella-resistant C57BL/10 mice or from the spleens of the susceptible BALB/c mice during the first week after infection. Treatment of control mice with the NK-reactive antibodies, however, decreased killing of the NK-sensitive target YAC-1, indicating that the NK cell depletion regimes were effective. Our results suggest that NK cells are not crucial for early control of B. abortus 2308 even though they may be activated following infection. Further experiments indicated that treatment of C57BL/10 mice with poly(A:U) did not decrease the number of brucellae recovered from their spleens although it did decrease the CFU in livers of mice infected with the high challenge dose.     

Endothelial cells and renal epithelial cells do not express the Wegener''s autoantigen, proteinase 3.

In vitro and in vivo T cell responses were determined during the course of bronchopulmonary infection with mucoid Pseudomonas aeruginosa. T cell responses were compared in two inbred mouse strains, namely BALB/c mice, which are resistant to the establishment of chronic bronchopulmonary Ps. aeruginosa infection, and C57Bl/6 mice, which have high numbers of bacteria in the lungs through 14 days post-infection. Unseparated lung cells and lung T cells from BALB/c mice exhibited significantly higher in vitro proliferative responses to both heat-killed Ps. aeruginosa and concanavalin A (Con A) than cells from C57Bl/6 mice through 20 days post-intratracheal infection with 10(4) colony-forming units (CFU) Ps. aeruginosa. Proliferation of unseparated lung cells but not lung T cells from BALB/c mice infected 6 days previously with 10(5) CFU Ps. aeruginosa was suppressed in response to Con A; these cells were unresponsive to specific antigen. Suppression of lymphocyte proliferation in the lungs of C57Bl/6 mice infected with 10(4) CFU Ps. aeruginosa and in BALB/c mice infected with 10(5) CFU was found to be mediated by adherent lung cells via the production of nitric oxide and prostaglandins. Determination of in vivo T cell-mediated responses in infected mice demonstrated that resistant BALB/c mice had high DTH and low Pseudomonas-specific antibody responses, while C57Bl/6 mice had low DTH and high antibody levels, in particular, IgG2b and IgM.