Role of different B-cell subsets in the specific and polyclonal immune response to T-independent antigens type 2.

Role of different B-cell subsets in the immune response to T-independent antigen type 2 (TI-2) was studied. BALB/c and C57BL/6 mice were immunized by polyvinylpyrrolidon (PVP), and the numbers of antibody- and Ig-forming cells (AFC and IFC, respectively) were determined by ELISPOT method. The number of cells producing non-specific Ig (nIFC) was calculated as the difference between the number of IFC and AFC; the number of nIFC induced by PVP was calculated as the difference between the number of nIFC in immune and control splenocytes. Immunization by PVP induced not only the AFC appearance, but also the increase in the number of the antigen-induced nIFC. The treatment of splenocytes by anti-CD5 antibodies and guinea pig complement reduced the increase in the numbers of newly formed AFC and nIFC to approximately 40% of control level. It means that CD5+ cells play an important role not only in the specific, but also in polyclonal immune response to non-self TI-2. To be sure that the decrease of AFC and nIFC numbers is due to depletion for CD5+ B-cells, but not CD5+ T-cells, splenocytes were separated to B-1 and B-2 subsets, and the numbers of AFC, IFC and nIFC were determined in each B-cell subpopulation separately. The overwhelming majority of newly formed AFC and nIFC was detected in B-1 subset. The numbers of AFC and nIFC in B-1 compartment was approximately 10-fold greater than in B-2 cells. A close parallelism between AFC and nIFC formation was observed. It is concluded that specific and polyclonal immune response to non-self TI-2-PVP-depends mainly on CD5+ B-1 subset.

Effects of corticosteroids on nerve root recovery after spinal nerve root compression.

Corticosteroids have been used in the treatment of radiculopathy and postoperative pain after lumbar disc surgery. Although the effects of steroids are thought to be antiinflammatory, the underlying nature of action may be more complex and may involve a direct effect on pain mediators like substance P. A feline model of nerve root compression and decompression was used to study the effect of steroids on the expression of cytokine differentiation antigens 4 and 5, and substance P. Ten adult cats were used. The animals were divided equally into a steroid treatment group and a control group. The sixth lumbar nerve root was compressed surgically and subsequently decompressed followed by local application of betamethasone or saline. The cats then were perfused and the corresponding nerve root and dorsal root ganglion were removed and immunostained for cytokine differentiation antigens 4 and 5, and substance P, respectively. The relative absence of cytokine differentiation antigens 4- and 5-labeled lymphocytes at the compression site in the steroid treated group is consistent with an antiinflammatory effect of the steroid. Substance P expression at the dorsal root ganglion in the steroid treated group was decreased significantly. These findings may help explain clinical observations of efficacy of steroids after spinal nerve root decompression.

Intravenous immune globulin effects on serum-soluble CD5 levels in atopic dermatitis.

BACKGROUND: Intravenous immune globulin (IVIG) therapy has been tried in the treatment of atopic dermatitis. Recently, the presence of serum-soluble CD5 (ssCD5) in atopic dermatitis was reported. OBJECTIVE: IVIG effects on ssCD5 levels in atopic dermatitis were examined and the correlation of ssCD5 level changes with clinical and laboratory parameters were investigated. METHODS: IVIG therapy was tried on 40 atopic dermatitis and 17 recurrent spontaneous abortion patients. Five atopic dermatitis patients received normal saline as a placebo control group. The clinical and laboratory parameters were evaluated on day 0, 1, 7 and 21 after administering the IVIG therapy. RESULTS: With IVIG therapy, in atopic dermatitis, the ssCD5 level was 5.5 +/- 6.2 ng/mL before infusion (day 0), 15.2 +/- 12.1 ng/mL on day 1, 13.8 +/- 14.1 ng/mL on day 7, and 3.9 +/- 4.1 ng/mL on day 21. The clinical severity score was 350.5 +/- 120.3 on day 0, 420.4 +/- 174.8 on day 1, 250.0 +/- 121.2 on day 7, and 115.5 +/- 53.9 on day 21. White blood cell (WBC) counts and serum IgE levels showed a gradual decrease with IVIG infusions. Blood eosinophil fractions were 5.3 +/- 2.8% on day 0, 8.6 +/- 5.2% on day 1, 7.3 +/- 3.7% on day 7, and 6.8 +/- 4.0% on day 21. Changes in the total eosinophil count were insignificantly parallel with those of blood eosinophil fractions CONCLUSION: In atopic dermatitis, IVIG therapy increased the ssCD5 levels. Further studies concerning the exact role of ssCD5 are needed.

Antigen receptor-mediated B cell death is blocked by signaling via CD72 or treatment with dextran sulfate and is defective in autoimmunity-prone mice.

Mature B cells undergo programmed cell death when surface (s) Ig is extensively multimerized. A signal that blocks death of B cells is thus required for activation of B cells in response to antigen stimulation. Here we show that only a few diverse transmembrane signals capable of inducing activation and proliferation of B cells blocked sig-mediated death of normal mature B cells, and that there is no correlation between mitogenic activity and the ability to rescue B cells from death. The results suggest that a specific signal is required for abrogating B cell death induced by sig cross-linking. Signaling via IL-4 receptor and CD40, both of which are derived from activated T cells, blocked sig-mediated death, as described previously. Signaling through a B cell antigen CD72, a counter-receptor of the pan-T antigen CD5, also blocked death of anti-Ig-treated mouse spleen B cells. CD72 signal may play a role in survival of B cells at the initial step of T-B interaction, where resting T cells recognize antigens presented by B cells. Moreover, B cell death by anti-Ig was blocked by T cell-independent antigens such as lipopolysaccharide and dextran sulfate, and spleen B cells from New Zealand mice, which are prone to autoantibody-dependent autoimmune diseases, were resistant to sig-mediated death. Mechanisms for blocking sig-mediated death may therefore be required in antibody response to foreign antigens regardless of T independence or T dependence and in autoantibody production.

Hormone regulation of murine T cells: potent tissue-specific immunosuppressive effects of thyroxine targeted to gut T cells.

Recent studies in athymic mice indicate that the neuroendocrine hormones thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) can significantly influence the development of lymphoid cells associated with intestinal intraepithelial lymphocytes (IEL). In the present study we have examined the effects of those hormones, as well as of thyroxine (T4), a thyroid-derived hormone regulated by TSH, on IEL development in euthymic mice. As reported here, whereas IEL in euthymic mice were unaffected by TRH and TSH treatment, T4 administered to adult euthymic mice at 3 or 6 weeks of age caused a dramatic reduction in the numbers of TCR alpha beta, CD8 alpha beta IEL, i.e. the same subsets previously shown to be up-regulated ty TRH and TSH in athymic mice. When given to euthymic mice >8 weeks of age, after TCR alpha beta and CD8 alpha beta subsets had reached normal levels, T4 had minimal effect on IEL, suggesting that the mode of action of T4 is directed to developing but not mature IEL. That possibility was confirmed in experiments in which T4 treatment of bone marrow radiation chimeras during an active phase of T cell regeneration temporarily halted all IEL development at a stage characteristic of immature IEL. Most interesting, the immunosuppressive effects of T4 were selectively targeted to the intestinal immune system since T4 had no effect on developing thymocytes or on mature peripheral T cells, in either normal euthymic mice or during hematopoietic reconstitution of radiation chimeras. These findings have implications for understanding intestinal immunity and disease, including chronic intestinal inflammation, in ways not previously appreciated.

Mononuclear cells in salivary glands of normal and isoproterenol-treated rats.

The purpose of this study was to analyse the phenotypical distribution of resident cells of the mononuclear phagocyte system in rat salivary glands, and to determine whether isoproterenol induces alterations in macrophage and lymphocyte surface-marker expression. Frozen sections of gland tissues were prepared from five normal rats, and from six rats treated with 20 mg/kg isoproterenol/day for 10 days. A panel of six monoclonal antibodies was used to identify membrane markers associated primarily with monocytes (ED1), mature tissue macrophages (ED2), lymphoid macrophages (ED3), MHC class II (Ia) antigens (OX6), CD5-positive T lymphocytes (OX19), and rat B lymphocytes (OX33). Double-labelling techniques were used to detect the coexpression of ED1/ED2 and OX6/ED2 mononuclear cell markers in the major salivary glands. ED2-positive macrophages were predominant in all three major glands, ranging from 96 cells/0.87 mm2 field in the parotid gland to 165 cells/0.87 mm2 in the submandibular. OX19-positive T lymphocytes were rarely observed in submandibular and parotid glands but represented a distinguishing feature of the sublingual. Moderate numbers of ED3-positive macrophages also were detected in sublingual tissues. In the submandibular and parotid glands, isoproterenol resulted in a decrease in ED2-positive cells, but ED2-positive macrophages increased in sublingual glands with isoproterenol. Isoproterenol resulted in a decrease in MHC class II antigen expression on submandibular and sublingual mononuclear cells but an induction of Ia antigen in the parotid gland. Double labelling revealed that isoproterenol induced coexpression of ED1/ED2 markers on mononuclear cells in the submandibular glands, but ED1/ED2-positive cells were absent from other glands. However, coexpression of MHC class II markers on ED2-positive cells in the sublingual and parotid glands of normal rats was frequently observed, with isoproterenol decreasing coexpression in the sublingual gland and increasing it in the parotid. B lymphocytes were not detected in any of the glands examined. These findings indicate that important differences exist in normal resident mononuclear cell subsets among the major salivary glands of the rat. The differential effects of isoproterenol on inflammatory cells may reflect important differences in local salivary gland immunoregulation. Although salivary gland inflammation induced by isoproterenol does not appear to result from immune mechanisms, the rich population of T lymphocytes and ED3-positive macrophages, and presence of MHC class II antigens, suggest that the sublingual gland may function as an immune organ and have a role in mucosal immunity.