C57BL/6 mice are more susceptible to antigen-induced pulmonary eosinophilia than BALB/c mice, irrespective of systemic T helper 1/T helper 2 responses

Inflammatory response differences between C57BL/6 and BALB/c mice following ovalbumin (OVA) sensitization and a single challenge were investigated. Serum immunoglobulin (Ig)E and IgG1 levels were higher in C57BL/6 mice than in BALB/c mice. In contrast, IgG2a levels in C57BL/6 mice were lower than in BALB/c mice. Furthermore, the number of eosinophils infiltrating into lungs in C57BL/6 mice was significantly higher than in BALB/c mice after OVA challenge. The levels of the T helper 2 (Th2)-type cytokines interleukin (IL)-4 and IL-5, generated in challenged C57BL/6 lung tissue, were also higher than in BALB/c lung tissue. The participation of IL-4 and IL-5 in the induction of eosinophil infiltration into the lungs was confirmed in both strains of mice by injection of anti-IL-4 and anti-IL-5 monoclonal antibodies (mAbs). However, following OVA stimulation, in vitro IL-4 and IL-5 production in splenocyte cultures from C57BL/6 mice was lower than in splenocyte cultures from BALB/c mice. These results indicate that C57BL/6 mice induce Th2-type responses in the lungs, while BALB/c mice induce T helper 1 (Th1)-type responses in the lungs, despite considerable production of IL-4 and IL-5 from splenocytes. Therefore, local immune responses are more important in the induction of allergic inflammation in the lungs and are different from systemic immune responses, which are thought to depend on genetic background.     

Differential susceptibility of C57BL/6 and DBA/2 mice to ovalbumin-induced pulmonary eosinophilia regulated by Th1/Th2-type cytokines

To test the effect of genotype on immune response, C57BL/6 and DBA/2 mice were sensitized with aluminum hydroxide gel (alum)-precipitated ovalbumin (OVA) and challenged with aerosolized OVA. The serum immunoglobulin (Ig) E and IgG1 levels in C57BL/6 mice were higher than those in DBA/2 mice. In contrast, IgG2a levels in C57BL/6 mice were lower than that in DBA/2 mice. C57BL/6 mice were also much more susceptible than DBA/2 mice to OVA-induced pulmonary eosinophilia. Furthermore, patterns of cytokine generation in lung tissue were different between C57BL/6 and DBA/2 mice after OVA challenge. Th2-type cytokine interleukin (IL-) 4 and IL-5 generation in C57BL/6 mice was higher than that in DBA/2 mice, while Thl-type cytokine interferon-gamma (IFN-gamma) generation in C57BL/6 mice was lower than that in DBA/2 mice. Similar patterns of IL-4 and IL-5, and IFN-gamma production in splenocytes from both strains after OVA stimulation in vitro were also observed. The participation of IL-4 and IL-5, and IFN-gamma in the regulation of eosinophil infiltration into the lung was confirmed by injection of anti-IL-5, -IL-4 and -IFN-gamma monoclonal antibodies. These results indicate that C57BL/6 mice preferentially induce IL-4 and IL-5-mediated Th2-type response, while DBA/2 mice induce IFN-gamma-mediated Thl-type response. Thus, the genotype of laboratory strains partially determines whether Th1- or Th2-type immune responses are elicited.     

Mechanism of mercury-induced autoimmunity: both T helper 1- and T helper 2-type responses are involved

Mercury can induce a systemic autoimmune disease in susceptible mouse strains. H-2s mice are particularly susceptible to mercury-induced autoimmunity and other mouse strains are more or less resistant. T helper 1/T helper 2 (Th1/Th2) dichotomy has been proposed for resistance or susceptibility, respectively. In the current study we show that mercury treatment induced a full autoimmune response in both C57BL/6 (H-2b) wild-type and interleukin-4 (IL-4)-deficient mice. Antibody production of all isotypes were induced, except that in IL-4-deficient mice there was no immunoglobulin E (IgE) and very low levels of immunoglobulin G1 (IgG1) antibody synthesis. Autoantibodies of different specificities were produced. The granular pattern of all IgG subclasses deposits were detected in the kidneys. In contrast to mercury-treated H-2s seconds mice, we did not detect any anti-nucleolar autoantibodies in the sera of mercury-treated wild-type or IL-4-deficient mice. To further explore the role of Th1/Th2 cytokines in the mercury model, we performed anti-interferon-gamma antibody treatment in IL-4-deficient mice together with mercury treatment and found that the production of IgG2a and IgG3, but not IgG2b, antibodies was downregulated. This indicated that besides Th2-type cytokines, Th1-type and other cytokines were involved as well in mercury-induced autoimmune response. Thus, C57BL/6 mice with H-2b genotype are highly susceptible to mercury-induced autoimmunity, and the genetic susceptibility to mercury involves more than a predisposition of a Th1-or Th2-type response.     

Induction of IgE responses using a recombinant mosquito salivary allergen rAed a 2 without adjuvant in mice.

BACKGROUND: Reactions to mosquito bites are a global problem. Several salivary proteins from Aedes (Ae.) aegypti, the most common mosquito species, have been cloned and expressed. Plasmid DNA vaccination has been shown to be effective in the downregulation of IgE responses. To investigate the in vivo antigenicity of these recombinant proteins and to study the mechanisms underlying plasmid DNA vaccination, a mouse model sensitized with a recombinant antigen has been developed. METHODS: BALB/c and C57BL/6 mice were injected intradermally with a 37-kD recombinant Ae. aegypti salivary allergen (rAed a 2) in the absence of adjuvant twice weekly for 8 weeks and then challenged twice with rAed a 2 at weeks 10 and 12. Serum rAed a 2-specific IgE, IgG1 and IgG2a were measured by ELISA. Intradermal tests were performed every 4 weeks. The binding capacity of rAed a 2-specific IgE to the native Aed a 2 was examined by immunoblotting. RESULTS: In both strains, sensitization with rAed a 2 induced a significant increase in IgE and IgG1, but not IgG2a. In all sensitized mice, a positive immediate skin reaction was apparent, while delayed-type hypersensitivity reactions were not observed. BALB/c mice produced significantly higher levels of IgE and IgG1 and larger wheals than C57BL/6 mice. The IgE antibodies elicited by rAed a 2 bound to not only rAed a 2 but also its natural form in mosquito saliva. CONCLUSION: (1) Repeated injections of rAed a 2 without adjuvant induce predominant Th2-type responses in mice. (2) BALB/c mice are better responders for IgE production than C57BL/6 mice. (3) rAed a 2 has identical allergenicity to its natural form.     

Priming of allergic immune responses by repeated ozone exposure in mice

The effects of repeated ozone exposures on the development of immune responses toward ovalbumin (OVA) were investigated in BALB/c and C57BL/6 mice. Ozone exposures (180 to 500 microg/m(3); 4 h, three times/wk for 4 wk) were combined with a protocol of OVA-aerosol exposure (1% OVA). Immediate cutaneous hypersensitivity (ICHS) reactions and antibody titers were assessed in parallel to cytokine levels of bronchoalveolar lavage fluids. In BALB/c mice, ozone triggered a T-helper (Th)2-like response indicated by dose-dependent increases in total serum immunoglobulin (Ig) E (from 133 to 821 ng/ml), interleukin (IL)-4 (from 60 to 208 pg/ml), and IL-5 levels (from 43 to 356 pg/ml), and by the recruitment of eosinophils and lymphocytes into the airways. Ozone exposure (500 microg/m(3)) in parallel to OVA-aerosol exposure increased anti-OVA IgG(1) antibody titers by 80%, leukotrienes (C(4)/D(4)/E(4)) by 60%, and airway responsiveness (11.3 versus 7.2 mg/ml methacholine), and doubled the frequency of positive ICHS reactions. In C57BL/6 mice, only the combination of OVA and ozone exposure induced positive ICHS reactions, doubled anti-OVA IgG(1), and suppressed anti-OVA IgG(2a) (-64%) antibody titers. Ozone, therefore, shifted the immune responses to OVA toward a Th2-like pattern in both "IgE-high responder" (BALB/c) and "IgE-low responder" (C57BL/6) mice.     

Self-priming cell culture system for monitoring genetically-controlled spontaneous cytokine-producing ability in mice

To monitor genetically-controlled cytokine-producing ability in mice in vitro, we developed a high-density cell culture system, which is preferable for inducing CD4+ T cell-dependent self-priming responses without any antigenic stimulation. When BALB/c spleen cells were cultured at high density (over 1.0 x 10(7) cells/well) in 12-well culture plate, they spontaneously produced cytokines including IFN-gamma, IL-2, IL-3, IL-5 and IL-6. The spontaneous cytokine production in this self-priming cell culture (SPCC) system was totally dependent on MHC class II-restricted CD4+ T cells. It was demonstrated that Th2-type BALB/c background mice exhibited higher levels of spontaneous cytokine production in SPCC culture compared with Th1-type C57BL/6 mice. Moreover, using BALB/c x C57BL/6 F1 mice and B10D2 congenic mice, it was demonstrated that highly spontaneous cytokine-producing ability in BALB/c background is genetically dominant and it is controlled by non-MHC genes. Unexpectedly, BALB/c mice spontaneously produced higher levels of IL-2 and IFN-gamma than C57BL/6 mice. However, BALB/c mice revealed lower levels of CTL and NK cell-generation in SPCC system compared with C57BL/6 mice. These results suggested that genetically-controlled predisposition of BALB/c mice toward Th2 immunity appeared not to be derived from their poor IFN-gamma-producing ability but rather derived from their poor responsiveness to IFN-gamma.     

The association between lung innate immunity and differential airway antigen- specific immune responses

The mechanisms involved in the differential regulation of airwayimmune responses in atopic versus non-atopic individuals arepoorly understood. In this study, the association between nonspecific immunity and the differential airway antigen-specificImmune responses was examined in a murine model. The disparityIn antigen-specific IgE and IgG2a productions between the twostrains of mice was observed to be significant. C57BL/6J micewere much more efficient than BALB/cJ mice in making IgE antibodyto Inhaled ovalbumin (OVA) antigen. On the contrary, BALB/cJmice did make more IgG2a antibodies than C57BL/6J mice to InhaledOVA. These findings suggest that in C57BL/6J mouse strain apredominant T_h 2 type of Immune response develops in responseto inhaled OVA antigen. In contrast, BALB/c mice mount a T_h1 type of immune response to aerosollzed OVA antigen. Furthermore,after lipopolysaccharlde (LPS) stimulation, the IL-12 mRNA expressionof lung-derived cells from BALB/cJ mice was higher than thatfrom C57BL/6J cells. However, the lung-derived cells of C57BL/6Jmice stimulated by LPS produced higher levels of IL-b and prostaglandinE than BALB/cJ lung-derived cells did. Therefore, our studydemonstrated that the difference of lung-derived cells in theirability to produce cytokine and prostaglandln between BALBIcJand C57BL/6J mice correlates well with the type of the airwayantigen-specific immune effector functions.     

Antibody and cytokine responses to the cilium-associated respiratory bacillus in BALB/c and C57BL/6 mice

The cilium-associated respiratory (CAR) bacillus is a gram-negative, gliding bacterium that causes persistent respiratory tract infections in rodents despite histologic and serologic evidence of a marked immune response. To assess humoral immunity and cytokine responses in CAR bacillus disease, 6-week-old female BALB/c and C57BL/6 mice were inoculated intratracheally with 10(5) CAR bacillus organisms. CAR bacillus-specific serum immunoglobulins (immunoglobulin M [IgM], IgG1, IgG2a, IgG2b, IgG3, and IgA) and local pulmonary cytokines (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], and interleukin-4 [IL-4]) were evaluated by enzyme-linked immunosorbent assay every 7 days for 49 days. BALB/c mice developed CAR bacillus-induced lesions early in the course of disease that became more severe with time. Correlating with increasing disease severity, BALB/c mice had elevations in all antibody isotypes tested, and elevations in pulmonary TNF-alpha, IFN-gamma, and IL-4. C57BL/6 mice developed mild lesions with mild increases in serum IgM, IgG1, IgG2b, and IgG3 levels and minimally detectable IgG2a and IgA. Cytokine perturbations were not detected in C57BL/6 mice. The persistence of infection in BALB/c mice with vigorous serum antibody responses and increased IFN-gamma and IL-4 responses suggests that humoral immunity and T-cell responses are ineffective at preventing CAR bacillus disease. Furthermore, the lackluster antibody responses and undetectable cytokine responses in C57BL/6 mice suggest that humoral immunity and T-cell responses are not critical in resistance to CAR bacillus-induced disease.     

Self-priming cell culture system for monitoring genetically-controlled spontaneous cytokine-producing ability in mice

To monitor genetically-controlled cytokine-producing ability in mice in vitro, we developed a high-density cell culture system, which is preferable for inducing CD4⁺ T cell-dependent self-priming responses without any antigenic stimulation. When BALB/c spleen cells were cultured at high density (over 1.0×10⁷ cells/well) in 12-well culture plate, they spontaneously produced cytokines including IFN-γ, IL-2, IL-3, IL-5 and IL-6. The spontaneous cytokine production in this self-priming cell culture (SPCC) system was totally dependent on MHC class II-restricted CD4⁺ T cells. It was demonstrated that Th2-type BALB/c background mice exhibited higher levels of spontaneous cytokine production in SPCC culture compared with Th1-type C57BL/6 mice. Moreover, using BALB/c×C57BL/6 F₁ mice and B10D2 congenic mice, it was demonstrated that highly spontaneous cytokine-producing ability in BALB/c background is genetically dominant and it is controlled by non-MHC genes. Unexpectedly, BALB/c mice spontaneously produced higher levels of IL-2 and IFN-γ than C57BL/6 mice. However, BALB/c mice revealed lower levels of CTL and NK cell-generation in SPCC system compared with C57BL/6 mice. These results suggested that genetically-controlled predisposition of BALB/c mice toward Th2 immunity appeared not to be derived from their poor IFN-γ-producing ability but rather derived from their poor responsiveness to IFN-γ.     

Antibody Production,Anaphylactic Signs,and T-Cell Responses Induced by Oral Sensitization With Ovalbumin in BALB/c and C3H/HeOuJ Mice

PurposeTwo mouse strains, BALB/c and C3H/HeOuJ, broadly used in the field of food allergy, were compared for the evaluation of the allergenic potential of ovalbumin (OVA).MethodsSensitization was made by administering 2 different OVA doses (1 and 5 mg), with cholera toxin as Th2-polarizing adjuvant. Antibody levels, severity of anaphylaxis, and Th1 and Th2 responses induced by the allergen were assessed. In addition, because the mice selected had functional toll-like receptor 4, the influence of contamination with lipopolysaccharide (LPS) on the immunostimulating capacity of OVA on spleen cells was also evaluated.ResultsBoth strains exhibited similar susceptibility to OVA sensitization. The 2 protein doses generated similar OVA-specific IgE and IgG1 levels in both strains, whereas C3H/HeOuJ mice produced significantly more IgG2a. Oral challenge provoked more severe manifestations in C3H/HeOuJ mice as indicated by the drop in body temperature and the severity of the anaphylactic scores. Stimulation of splenocytes with OVA led to significantly higher levels of Th2 and Th1 cytokines in BALB/c, and these were less affected by protein contamination with LPS.ConclusionsThe antibody and cytokine levels induced by OVA in BALB/c mice and the observation that BALB/c spleen cell cultures were more resistant than those of C3H/HeOuJ mice to the stimulus of LPS make this strain prone to exhibit Th2-mediated food allergic reactions and very adequate for the study of the features of OVA that make it allergenic.     

Autoreactive responses to environmental factors: 3. Mouse strain-specific differences in induction and regulation of anti-DNA antibody responses due to phthalate-isomers

Little is known of the role of specific environmental factors in promoting autoimmune disorders such as systemic lupus erythematosus (SLE). This study addresses how exposure to phthalates, common environmental factors in foods, and biomedical devices could affect the immune functions of resistant and autoimmune-prone mice. We have previously shown that immunization with ortho-phthalate evokes anti-DNA antibody in BALB/c and NZB/W F1 mice, but only the latter suffer from nephritis and high mortality. BALB/c mice, in contrast, develop idiotype-specific CD8+ suppressor T cells downregulating autoreactive B cells. Here we report that all phthalate-isomers (ortho-, meta- and para-) are capable of inducing anti-DNA antibody responses and SLE-like syndromes. Kidney pathology worsens in NZB/W F1 and to a degree, in C57BL/6 mice after repeated exposure to phthalates. Only BALB/c and DBA/2 overcome adverse autoreactivity by induction of Ts cells; but in vivo depletion of these T cells renders these strains susceptible to autoreactivity. Anti-DNA antibodies in affected NZB/W F1 are largely IgG2a-type, while in BALB/c, DBA/2, and C57BL/6 mice IgG1-type. This is further corroborated by cytokine analyses that imply corresponding Th1/Th2 involvement. In summary, the commonly used phthalates appear harmful to susceptible strains, while BALB/c and DBA/2 are spared due to induction of Ts cells.     

Non-major histocompatibility complex control of antibody isotype and Th1 versus Th2 cytokines during experimental infection of mice with Mycobacterium avium

Infection of different strains of mice with Mycobacterium avium has revealed genetic control of the immunoglobulin isotype induced and of the balance between Th1 and Th2 cytokines. Female BALB/c or C57BL/10 mice were infected intranasally with 10(5) M. avium organisms. The antibody response was measured over 18 weeks by enzyme-linked immunosorbent assay and Western blotting, while numbers of cytokine-producing cells were assessed at 12 to 15 weeks by ELISPOT assay. Upon infection, C57BL/10 mice produced a clear Th1 response with strong gamma interferon (IFN-gamma) production, no interleukin-4 (IL-4), and almost entirely immunoglobulin G2a (IgG2a) antibody. In contrast, BALB/c mice developed T cells producing IL-4, as well as those producing IFN-gamma, while the antibody response was a mixture of IgG1 and IgG2a. Antibodies from BALB/c mice were also able to recognize a greater range of antigens than were C56BL/10 mice. B10D2 mice, which carry the BALB/c major histocompatibility complex haplotype on a C57BL/10 background, followed the C57BL/10 cytokine pattern. Mice infected with Listeria monocytogenes did not show a similar response dichotomy.     

Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and BALB/c mice

Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium implicated as a putative etiologic agent of sarcoidosis. To characterize the pulmonary immune response to PA, C57BL/6 and BALB/c mice were intraperitoneally sensitized and intratracheally challenged with heat-killed bacteria. C57BL/6 mice challenged with PA developed a cellular immune response characterized by elevations in Th1 cytokines/chemokines, increased numbers of lymphocytes and macrophages in lung lavage fluid, and peribronchovascular granulomatous inflammation composed of T- and B-lymphocytes and epithelioid histiocytes. T-lymphocytes in the lung lavage fluid showed a marked CD4+ cell predominance. In contrast, C57BL/6 mice challenged with Staphylococcus epidermidis (SE), another gram-positive commensal of human skin, and BALB/c mice challenged with PA, showed only a modest induction of Th1 cytokines, less pulmonary inflammation, and no granulomatous changes in the lung. Enhancement of Toll-like receptor expression was seen in PA-exposed C57BL/6 mice within 24 h after exposure, suggesting that induction of innate immunity by PA contributes to the robust, polarized Th1 immune response elicited by this bacterium. These findings suggest that PA-induced pulmonary inflammation may be a useful model for testing the contributions of both bacterial and host factors in the development, maintenance, and resolution of granulomatous inflammation in the lung.     

Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic islets of C57BL/6 and BALB/c mice by multiple low doses of streptozotocin

In the nonobese diabetic (NOD) mouse, the T helper (Th)1-type inflammatory cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha play a critical role in the development of type 1 diabetes, whereas the Th2-type anti-inflammatory cytokines interleukin (IL)-4 and IL-10 operate counterregulatory. There are no comprehensive analyses on cytokine profiles in the mouse model of diabetes induced with multiple low doses of streptozotocin (MLD-STZ). Therefore, we used islets to study ex vivo effects of MLD-STZ and in vitro effects of STZ on IFN-gamma, TNF-alpha, IL-4, and IL-10 on both levels of protein-producing cells and the mRNA expression, as well as the mRNA expression of the Th3-type cytokine transforming growth factor TGF-beta1. C57BL/6 and BALB/c mice of both genders were injected intraperitoneally with 40 mg/kg body wt STZ on five consecutive days and islets were isolated on day I and 3 after the fifth STZ-injection. Control mice received the solvent of STZ. In islets of C57BL/6 mice of both genders MLD-STZ similarly stimulated production of IFN-gamma and TNF-alpha, but significantly reduced IL-4 and IL-10 levels in male mice only. Opposite results were obtained in islets of BALB/c mice of both genders. Here, MLD-STZ markedly decreased the levels of IFN-gamma and TNF-alpha, but significantly increased the levels of IL-4 and IL-10. The functional results were in line with MLD-STZ effects on the mRNA expression of the cytokines. Moreover, MLD-STZ effects on the TGF-beta1 mRNA expression were reversed to the effects on IFN-gamma and TNF-alpha. The in vitro effects of STZ in islets, in general, were similar to those exerted by MLD-STZ. Apparently, reduction and upregulation of Th2-type cytokines was more associated with susceptibility and resistance, respectively, to MLD-STZ-induced diabetes than upregulation of Th1-type cytokine levels.     

Genetically programmed biases in Th1 and Th2 immune responses modulate atherogenesis

Atherosclerotic lesions contain T lymphocytes, which orchestrate adaptive immunity and regulate many innate immune pathways. This study examined the influence of Th1 and Th2 helper cell subsets on atherogenesis in two ApoE(-/-) mouse strains, C57BL/6 and BALB/c, which display opposite T-cell subset polarizations. ApoE(-/-) BL/6 mice showed predominant Th1-like immune responses on polyclonal stimulation of splenic CD4(+) T cells and had IgG2a antibodies to oxidized low-density lipoprotein (a disease-related antigen) whereas ApoE(-/-) BALB/c mice displayed predominant Th2 responses by CD4(+) T cells and an IgG1 isotype response toward oxidized low-density lipoprotein. ApoE(-/-) BL/6 and BALB/c mice consumed a high-cholesterol diet for 10, 16, and 24 weeks with equivalent cholesterolemic responses. The Th1-slanted BL/6 mice developed significantly more atherosclerosis in the aortic root and abdominal aorta at all time points compared with BALB/c mice, supporting a proatherogenic role for Th1 response. Progression of atherosclerosis was associated with increased levels of interleukin (IL)-6 in mouse serum and CD4(+) T-cell culture supernatants and increased levels of the acute-phase protein, serum amyloid A (SAA). Both IL-6 and SAA levels rose significantly in ApoE(-/-) BL/6 mice compared with BALB/c mice. The circulating cytokine milieu (IL-6) and acute phase reactants such as SAA may reflect alterations in the Th1/Th2 balance. The results presented here illustrate how genetically determined modifiers of both immune and inflammatory responses can modulate atherogenesis independently of lipid levels.     

Neutrophil depletion exacerbates experimental Chagas' disease in BALB/c, but protects C57BL/6 mice through modulating the Th1/Th2 dichotomy in different directions

To elucidate the roles of neutrophils in experimental Chagas' disease, we depleted the peripheral neutrophils in BALB/c and C57BL/6 mice with a monoclonal antibody 1 day before Trypanosoma cruzi infection. Neutrophil depletion in BALB/ c mice resulted in exacerbation of the disease and decreased expression of mRNA for Th1 cytokines, including IL-2 and IFN-gamma, IL-12p40 and TNF-alpha in their spleens after the infection, while a Th2 cytokine, IL-10, increased especially 1 day after infection. Neutrophils from infected BALB / c mice expressed mRNA for IL-12p40, IFN-gamma, TNF-alpha and Th1 chemoattractive chemokines, monokine induced by IFN-gamma (MIG) and macrophage inflammatory protein-1alpha (MIP-1alpha ). In contrast, in C57BL/6 mice neutrophil depletion induced resistance to the disease and enhanced the expression of the above Th1 cytokines, although IL-10 mRNA in neutrophil-depleted C57BL/6 mice was also higher than in control mice. Neutrophils from C57BL/6 mice did not express IL-12p40, IFN-gamma and MIG but expressed TNF-alpha, MIP-1alpha and IL-10. Therefore, neutrophils may play opposite roles in these two strains of mice with respect to protection versus exacerbation of T. cruzi infection, possibly through modulating the Th1/Th2 dichotomy in different directions.     

Inflammatory response and dynamics of lung T cell subsets in Th1, Th2 biased and Th2 deficient mice during the development of hypersensitivity pneumonitis

It is considered that hypersensitivity pneumonitis (HP) occurs with a Th1 cell dominance; however, the role of Th1/Th2 balance is still unclear. C57BL/6 (Th1-biased), BALB/c wt (Th2-biased) and BALB/c Stat6?/? (Th2 deficient) mice were treated with Saccharopolyspora rectivirgula (SR) or saline during 3 weeks, and sacrificed 1 and 4 days (early and late response) after the last administration. Lung isolated T cell subpopulations were analyzed and lung damage extent was quantified. C57BL/6 wt mice exhibited a significant increase in the extent of lung damage when sacrificed at 4 days compared with those sacrificed 1 day after the last SR administration. In contrast, BALB/c wt mice showed a progressive decrease in the extent of lung damage. A significant increase of NKT CD4+ subset was found in C57BL/6 mice while NKT DN cells were increased in BALBc wt mice. Also, NK and γδ T cells were increased in BALB/c mice at 1 and 4 days. Stat6?/? mice behave similar to the C57BL/6 mice, showing a progressive increase in the extent of lung damage. A significant increase in the levels of Th1 and Th2 cytokines was observed in bronchoalveolar lavage from the SR-treated mice. These results confirm a predominant role of the Th1 response in HP and suggest that the control of inflammation by Th2 biased mice may be related with the increase of NKT DN cells and regulatory NK and γδ T cells.