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218 Mechanisms of increased IgE synthesis in acute graft vs. host disease (GVHD)
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THE DIAGNOSTIC SIGNIFICANCE OF INCREASED BRONCHIAL RESPONSIVENESS TO METHACHOLINE IN SUBJECTS WITH RHINITIS. E.H. Ramsdale, B.M., M. Morris, and Hamilton, Ontario, Canada. Some people e.g. with rhinitis, who have not been recognized to have asthma, have an increase in bronchial responsiveness to methacholine. We have investigated the diagnostic significance of this finding with respect to the presence of asthma in 20 subjects with rhinitis and 10 without. Bronchial responsiveness to methacholine (Juniper et al., Thorax 1978;33:705-18) and isocapnic hyperventilation of cold air (O'Byrne et al., Am. Rev. Respir. Dis. 1982;125:281-5), the change in FEVl with salbutamol (200 ug), and diurnal variation in peak flow rates (Ryan et al., Thorax 1982;37:423-9) were measured in each subject. The response to salbutamol was normal in all subjects. Diurnal variation was increased only in 3 of 6 subjects with PC20 2-8 mg/ml. FEVl fell in response to isocapnic hyperventilation of cold air in 1 of 4 subjects with PC20 8-20 mg/ml and 3 of 6 subjects with PC20 2-8 mg/ml. These results suggest that when the PC20 is within the asthmatic range (<20 mg/ml) some people have asthma which has not been recognized, some will have potential asthma which can be triggered by vigorous stimuli, and some The results suggest that will have no asthma. there is a continuum of bronchial responsiveness between normals and asthmatics, and that symptoms are more likely to occur if the PC20 is less than 8 mg/ml.
MECHANISMS OF INCREASED IGE SYNTHESIS IN ACUTE GRAFT VS. HOST DISEASE (GVHD). J.A. SARYAN, D.Y.M. LEUNG, J. RAPPAPORT, R. PARKMAN, R.S. GENA, BOSTON, MA. The --in vitro regulation of IgE synthesis by peripheral blood lymphocytes (PBL) from seven patients receiving allogeneic histocompatible bone marrow transplantation was studied. Synthesis of IgE, but not of IgG was elevated in cultures of PBL obtained during acute GVHD (17,923 + 14,607 pg/lO6 cells) but not in cultures-of PBL obtained after resolution of the acute GVHD when serum IgE levels had returned to normal (106 2 31 pg/lO6 cells). The increased synthesis of IgE was suppressed by normal allogeneic T lymphocytes belonging to the T3+, T8+, T4- subset and by autologous T lymphocytes obtained after the resolution of GVHD suggesting that there was a deficiency in IgE-specific Patients suppressor T cells during acute GVHD. lymphocytes obtained during acute GVHD had normal or elevated numbers of T8+ cells but the majority of these cells failed to express the Patient's 'T3 antigen present on mature T cells. T cells but not normal T cells spontaneously secreted a factor which increased IgE, but not IeG. svnthesis by normal B cells indicating the p;esence of --in viva activated IgE specific helper T cells in acute GVHD. The results obtained indicate that an imbalance in IgE specific immunoregulatory T cells. consisting of activated helper T cells and decreased suppressor T cells, may account for the elevation of serum IgE levels in patients with acute GVHD.
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REGULATION OF SPONTANEOUS IN VITRO IgE SYNTHESIS BY AUTOLOGOUS ECZEMA AND ALLOGENEIC NONATOPIC T CELL SUBSETS. Z.Hemady,M.D.,M.Chambers,B.S., S. Gellis, M.D., and R.E.Rocklin,M.D.,Boston, MA. Eczema B cells were co-cultured with either autologous or allogeneic T cells in RPM1 1640 with 10% FCS at 0.75 x 10' cells/ml (B/T=0.5)and supernatant IgE measured by a modified PRIST assay. Net IgE synthesis was obtained by subtracting preformed IgE (+cycloheximide at day 0) from total IgE in 7 day supernatants. T cells were either untreated, heat-killed (56' for 45 min.), exposed to 2000 RADS, or depleted of helper/suppressor T cells by "panning" with monoclonal antibodies (Leu 3a and Leu 2a-BectonDickinson). Atopic eczema B cells spontaneously synthesized IgE when cultured alone. Co-culturing autologous T cells with atopic eczema B cells resulted in insignificant suppression of net IgE synthesis (Mean suppression=2%). However, in allogeneic recombinations, control T cells significantly suppressed net IgE synthesis by atopic eczema B cells (Mean suppression=50%; P 0.05). This suppression was abrogated if allogeneic control T cells were heat-killed, irradiated (2000 RADS) or depleted of Leu 2a+ suppressor T cells. As compared to untreated T cells, allogeneic T cells depleted of Leu 3a+ helper cells had an increased suppressive effect on net IgE synthesis by atopic eczema B cells (mean suppression=60%). We conclude that in contrast to autologous eczema T cells, nonatopic T cells induce significant suppression of spontaneous IgE synthesis by atopic eczema B cells and that this inhibition is mediated by a radiation-sensitive, Leu 2af T cell subset.
OF IGE ANTIBODY SYNTHESIS IN MAN BY ANTIIDIOTYPIC ANTIBODIES, R.S. GEHA AND M. COMUNALE, BOSTON, MA. The effect of rabbit antiidiotypic antisera raised against human F(ab')Z fragments of tetanus toxoid (TT) antibodies on the --in vitro synthesis of TT specific IgE antibody by peripheral blood lymphocytes (PBL) was examined in three subjects. Two of these subjects were allergic twins whose sera persistently contained IgE anti TT antibodies. The third subject was a non allergic individual who had a slightly elevated serum IgE (250 I.LJ./ml) and who following booster immunization with TT exhibited a transient serum IgE anti TT response. After appropriate absorption rabbit anti Id IgG reacted with anti TT antibodies of both IgG and IgE isotypes in an idiotype specific and antigen specific fashion. PBL and B cells from the three subjects studied spontaneously synthesized TT specific IgE in In all three cases, adsorption of B culture. cells over plastic plates coated with anti Id prior to culture specifically decreased the synthesis of IgE antibodies to TT but did not affect the synthesis of IgE antibodies to ragweed antigen E by PBL from the twin allergic subjects. Addition of anti Id to cultures of PBL from all three subjects specifically inhibited the synthesis of TT specific IgE. This inhibition was shown to be exerted both at the level of the B cells and via the generation of antigen specific suppressor T cells from radiosensitive precursors. The results indicate that the synthesis of antigen specific IgE in man is subject to regulation by idiotypic antiidiotypic interactions which can involve both B and T cells. RmnxrIoN
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THE DIAGNOSTIC SIGNIFICANCE OF INCREASED BRONCHIAL RESPONSIVENESS TO METHACHOLINE IN SUBJECTS WITH RHINITIS. E.H. Ramsdale, B.M., M. Morris, and Hamilton, Ontario, Canada. Some people e.g. with rhinitis, who have not been recognized to have asthma, have an increase in bronchial responsiveness to methacholine. We have investigated the diagnostic significance of this finding with respect to the presence of asthma in 20 subjects with rhinitis and 10 without. Bronchial responsiveness to methacholine (Juniper et al., Thorax 1978;33:705-18) and isocapnic hyperventilation of cold air (O'Byrne et al., Am. Rev. Respir. Dis. 1982;125:281-5), the change in FEVl with salbutamol (200 ug), and diurnal variation in peak flow rates (Ryan et al., Thorax 1982;37:423-9) were measured in each subject. The response to salbutamol was normal in all subjects. Diurnal variation was increased only in 3 of 6 subjects with PC20 2-8 mg/ml. FEVl fell in response to isocapnic hyperventilation of cold air in 1 of 4 subjects with PC20 8-20 mg/ml and 3 of 6 subjects with PC20 2-8 mg/ml. These results suggest that when the PC20 is within the asthmatic range (<20 mg/ml) some people have asthma which has not been recognized, some will have potential asthma which can be triggered by vigorous stimuli, and some The results suggest that will have no asthma. there is a continuum of bronchial responsiveness between normals and asthmatics, and that symptoms are more likely to occur if the PC20 is less than 8 mg/ml.
MECHANISMS OF INCREASED IGE SYNTHESIS IN ACUTE GRAFT VS. HOST DISEASE (GVHD). J.A. SARYAN, D.Y.M. LEUNG, J. RAPPAPORT, R. PARKMAN, R.S. GENA, BOSTON, MA. The --in vitro regulation of IgE synthesis by peripheral blood lymphocytes (PBL) from seven patients receiving allogeneic histocompatible bone marrow transplantation was studied. Synthesis of IgE, but not of IgG was elevated in cultures of PBL obtained during acute GVHD (17,923 + 14,607 pg/lO6 cells) but not in cultures-of PBL obtained after resolution of the acute GVHD when serum IgE levels had returned to normal (106 2 31 pg/lO6 cells). The increased synthesis of IgE was suppressed by normal allogeneic T lymphocytes belonging to the T3+, T8+, T4- subset and by autologous T lymphocytes obtained after the resolution of GVHD suggesting that there was a deficiency in IgE-specific Patients suppressor T cells during acute GVHD. lymphocytes obtained during acute GVHD had normal or elevated numbers of T8+ cells but the majority of these cells failed to express the Patient's 'T3 antigen present on mature T cells. T cells but not normal T cells spontaneously secreted a factor which increased IgE, but not IeG. svnthesis by normal B cells indicating the p;esence of --in viva activated IgE specific helper T cells in acute GVHD. The results obtained indicate that an imbalance in IgE specific immunoregulatory T cells. consisting of activated helper T cells and decreased suppressor T cells, may account for the elevation of serum IgE levels in patients with acute GVHD.
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REGULATION OF SPONTANEOUS IN VITRO IgE SYNTHESIS BY AUTOLOGOUS ECZEMA AND ALLOGENEIC NONATOPIC T CELL SUBSETS. Z.Hemady,M.D.,M.Chambers,B.S., S. Gellis, M.D., and R.E.Rocklin,M.D.,Boston, MA. Eczema B cells were co-cultured with either autologous or allogeneic T cells in RPM1 1640 with 10% FCS at 0.75 x 10' cells/ml (B/T=0.5)and supernatant IgE measured by a modified PRIST assay. Net IgE synthesis was obtained by subtracting preformed IgE (+cycloheximide at day 0) from total IgE in 7 day supernatants. T cells were either untreated, heat-killed (56' for 45 min.), exposed to 2000 RADS, or depleted of helper/suppressor T cells by "panning" with monoclonal antibodies (Leu 3a and Leu 2a-BectonDickinson). Atopic eczema B cells spontaneously synthesized IgE when cultured alone. Co-culturing autologous T cells with atopic eczema B cells resulted in insignificant suppression of net IgE synthesis (Mean suppression=2%). However, in allogeneic recombinations, control T cells significantly suppressed net IgE synthesis by atopic eczema B cells (Mean suppression=50%; P 0.05). This suppression was abrogated if allogeneic control T cells were heat-killed, irradiated (2000 RADS) or depleted of Leu 2a+ suppressor T cells. As compared to untreated T cells, allogeneic T cells depleted of Leu 3a+ helper cells had an increased suppressive effect on net IgE synthesis by atopic eczema B cells (mean suppression=60%). We conclude that in contrast to autologous eczema T cells, nonatopic T cells induce significant suppression of spontaneous IgE synthesis by atopic eczema B cells and that this inhibition is mediated by a radiation-sensitive, Leu 2af T cell subset.
OF IGE ANTIBODY SYNTHESIS IN MAN BY ANTIIDIOTYPIC ANTIBODIES, R.S. GEHA AND M. COMUNALE, BOSTON, MA. The effect of rabbit antiidiotypic antisera raised against human F(ab')Z fragments of tetanus toxoid (TT) antibodies on the --in vitro synthesis of TT specific IgE antibody by peripheral blood lymphocytes (PBL) was examined in three subjects. Two of these subjects were allergic twins whose sera persistently contained IgE anti TT antibodies. The third subject was a non allergic individual who had a slightly elevated serum IgE (250 I.LJ./ml) and who following booster immunization with TT exhibited a transient serum IgE anti TT response. After appropriate absorption rabbit anti Id IgG reacted with anti TT antibodies of both IgG and IgE isotypes in an idiotype specific and antigen specific fashion. PBL and B cells from the three subjects studied spontaneously synthesized TT specific IgE in In all three cases, adsorption of B culture. cells over plastic plates coated with anti Id prior to culture specifically decreased the synthesis of IgE antibodies to TT but did not affect the synthesis of IgE antibodies to ragweed antigen E by PBL from the twin allergic subjects. Addition of anti Id to cultures of PBL from all three subjects specifically inhibited the synthesis of TT specific IgE. This inhibition was shown to be exerted both at the level of the B cells and via the generation of antigen specific suppressor T cells from radiosensitive precursors. The results indicate that the synthesis of antigen specific IgE in man is subject to regulation by idiotypic antiidiotypic interactions which can involve both B and T cells. RmnxrIoN