Rush immunotherapy results in allergen-specific alterations in lymphocyte function and interferon-γ production in CD4+ T cells Gideon Lack, MD, Harold.

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Rush immunotherapy results in allergen-specific alterations in lymphocyte function and interferon-γ production in CD4+ T cells Gideon Lack, MD, Harold S. Nelson, MD, David Amran, MD, Akihiro Oshiba, MD, Thomas Jung, MD, Katherine L. Bradley, BSc, Patricia C. Giclas, PhD, Erwin W. Gelfand, MD Journal of Allergy and Clinical Immunology Volume 99, Issue 4, Pages 530-538 (April 1997) DOI: 10.1016/S0091-6749(97)70081-2 Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 1 RIT decreases allergen-specific cutaneous reactivity. Ten subjects underwent skin testing with Dpt and cat extracts in increments of 1/2 log unit (range, 1 to 10,000 AU/ml). Subjects were tested before RIT and after maintenance doses were reached. Expressed along the y axis is change in log concentration of extract after RIT that elicited a positive skin test response. *p < 0.01 compared with pretreatment levels. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 2 RIT decreases allergen-specific nasal reactivity. Four subjects had nasal challenges to Dpt and cat extracts with the same concentrations of extract and at the same time points as for skin testing. Expressed along the y axis is change in log concentration of extract required to cause a positive response to nasal challenge after RIT. p < 0.01 compared with pretreatment levels. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 3 RIT causes an increase in allergen-specific IgE in serum. Determination of allergen-specific IgE in serum was by RAST. Expressed along the y axis are serum RAST values for cat and Dpt (in kilounits per milliliter). p H 0.01 compared with pretreatment levels. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 4 RIT causes an allergen-specific increase in IgG4. Determination of antibody levels to cat and Dpt was done by ELISA. Shown are serum concentrations of anti-cat IgG1 (A), anti-Dpt IgG1 (B), anti-cat IgG4 (C), and anti-Dpt IgG4 (D), expressed in units of optical density (O.D.). p < 0.01 compared with pretreatment levels. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 4 RIT causes an allergen-specific increase in IgG4. Determination of antibody levels to cat and Dpt was done by ELISA. Shown are serum concentrations of anti-cat IgG1 (A), anti-Dpt IgG1 (B), anti-cat IgG4 (C), and anti-Dpt IgG4 (D), expressed in units of optical density (O.D.). p < 0.01 compared with pretreatment levels. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 4 RIT causes an allergen-specific increase in IgG4. Determination of antibody levels to cat and Dpt was done by ELISA. Shown are serum concentrations of anti-cat IgG1 (A), anti-Dpt IgG1 (B), anti-cat IgG4 (C), and anti-Dpt IgG4 (D), expressed in units of optical density (O.D.). p < 0.01 compared with pretreatment levels. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 4 RIT causes an allergen-specific increase in IgG4. Determination of antibody levels to cat and Dpt was done by ELISA. Shown are serum concentrations of anti-cat IgG1 (A), anti-Dpt IgG1 (B), anti-cat IgG4 (C), and anti-Dpt IgG4 (D), expressed in units of optical density (O.D.). p < 0.01 compared with pretreatment levels. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 5 RIT causes an allergen-specific decrease in lymphocyte proliferation. Lymphocyte proliferative responses to cat and Dpt allergens were measured in four patients before and after RIT. Expressed along the y axis is stimulation index (S.I.) for cat (A) and Dpt stimulation (B). Background response for the four patients was 3544 ± 496 cpm. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 5 RIT causes an allergen-specific decrease in lymphocyte proliferation. Lymphocyte proliferative responses to cat and Dpt allergens were measured in four patients before and after RIT. Expressed along the y axis is stimulation index (S.I.) for cat (A) and Dpt stimulation (B). Background response for the four patients was 3544 ± 496 cpm. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 6 RIT causes a decrease in the CD4:CD8 ratio. Lymphocyte subset analysis was done on PBMCs from 10 patients before and after maintenance doses of RIT were reached. Expressed along the y axis is the CD4:CD8 ratio for each patient. p < 0.05 compared with pretreatment levels. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 7 RIT causes an increase in serum IFN-γ levels and in frequency of IFN-γ–producing T cells. IFN-γ was measured in serum by ELISA and by intracellular staining in activated CD3+ T cells. Shown are serum concentrations of IFN-γ for seven patients (A) and percentages of CD3+ T cells producing IFN-γ (B) before and after maintenance dose of RIT was reached. p < 0.05 compared with pretreatment values. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 7 RIT causes an increase in serum IFN-γ levels and in frequency of IFN-γ–producing T cells. IFN-γ was measured in serum by ELISA and by intracellular staining in activated CD3+ T cells. Shown are serum concentrations of IFN-γ for seven patients (A) and percentages of CD3+ T cells producing IFN-γ (B) before and after maintenance dose of RIT was reached. p < 0.05 compared with pretreatment values. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 8 RIT causes a selective increase in IFN-γ production by the CD4+ T-cell population. The percentage of IFN-γ–producing cells was analyzed in different T-cell subsets. Expressed is percentage of IFN-γ–producing CD4+ T cells (A) and CD8+ T cells (B) before and after maintenance dose of RIT was reached. p < 0.01 compared with pretreatment values. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions

Figure 8 RIT causes a selective increase in IFN-γ production by the CD4+ T-cell population. The percentage of IFN-γ–producing cells was analyzed in different T-cell subsets. Expressed is percentage of IFN-γ–producing CD4+ T cells (A) and CD8+ T cells (B) before and after maintenance dose of RIT was reached. p < 0.01 compared with pretreatment values. Journal of Allergy and Clinical Immunology 1997 99, 530-538DOI: (10.1016/S0091-6749(97)70081-2) Copyright © 1997 Mosby, Inc. Terms and Conditions