Upregulation of B7.2, but not B7.1, on B cells from patients with allergic asthma

doi:10.1016/S0091-6749(98)70199-X

Journal of Allergy and Clinical Immunology

Volume 101, Issue 1, January 1998, Pages 96-102

https://doi.org/10.1016/S0091-6749(98)70199-X Get rights and content

Abstract

Background: Allergic asthma is associated with T_H2-like cell responses and increased IgE production. Recent studies in mice have suggested that the costimulatory molecule B7.2 (CD86) may influence the development of T_H2 cells. Objective: We sought to determine the potential role of B7.2 in patients with asthma. Methods: We performed an analysis of B cells from patients with allergic asthma and healthy control subjects for expression of B7.1 and B7.2 on B cells using five-parameter flow cytometry. Results: We report that atopic patients with asthma who are exposed to allergens have significantly (p < 0.005) higher levels of B7.2 expression on B cells than atopic asthmatic subjects not exposed to allergen in vivo or nonatopic control subjects. In contrast, there were no differences in B7.1 (CD80) expression among the three study subject groups. When peripheral blood mononuclear cells from asthmatic patients or normal control subjects were stimulated with IL-4 or IL-13, the expression of B7.2, but not B7.1, was significantly increased (p < 0.005) on B cells. Interferon-γ or IL-12 did not affect the expression of either molecule. The functional significance of B7.2 induction by IL-4 in allergic disease was suggested by the increased expression of this molecule on CD23+, but not CD23−, B cells. Conclusion: These results indicate that the same B cell involved in allergen presentation also expresses the costimulatory molecule B7.2 and support the hypothesis that this molecule is an important costimulatory molecule in allergic responses, the expression of which can be modulated by T_H2-like cytokines. (J Allergy Clin Immunol 1998;101:96-102.)

Section snippets

Reagents

Anti-B7.1 and anti-B7.2 antibodies (IgG1) were purchased from Ancell (Bayport, Minn.). Recombinant human IL-4 (rIL-4) was obtained from Schering Research Institute (Bloomfield, N.J.). Human rIL-13 was obtained from Peprotech (Rocky Hill, N.J.), recombinant interferon-γ (rIFN-γ) from Genentech Inc. (San Francisco, Calif.), and rIL-12 from R&D Systems (Minneapolis, Minn.). The following monoclonal antibodies were obtained from Becton Dickinson Immunocytometry Systems (San Jose, Calif.): anti-CD19

Increased expression of B7.2 on B cells of atopic patients with asthma

Freshly isolated PBMCs from patients with atopic asthma and normal control subjects were analyzed by flow cytometry for the expression of B7.1, B7.2, and CD23 on B cells. As shown in Fig. 1, A, B7.2 expression was significantly higher on B cells from asthmatic patients exposed to allergen (63.3% ± 2.9%) compared with nonatopic control subjects (34.1% ± 4.1%, p < 0.005).

. B7.2 and CD23, but not B7.1, expression on B cells is increased in asthmatic patients exposed to allergen. Freshly isolated

DISCUSSION

Costimulation through the B7/CD28 pathway plays a critical role in the establishment of antigen-driven immune responses.¹ Antigen-specific immune responses are initiated after the interaction between T cells and antigen-presenting cells such as B cells. T-cell activation occurs after two signals. The first signal is the interaction between the T-cell receptor and major histocompatibility complex class II molecules. The second signal involves accessory molecules such as CD28 and B7. CD28 has

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CD86 plays an important role in allergic diseases and has been shown to be up-regulated on B cells from allergic patients (Bellou and Finn 2005). Also, CD86 is essential for development of IL-4 producing T cells which directs their polarization toward type 2 (Hofer et al. 1998). In the present study, DCs from cockroach-allergic patients upon Per a 10 stimulation demonstrated a significantly high expression of CD80 and CD86 as compared to the DCs from healthy individuals or other-allergic patients.
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CD-80 has been found to play a key role in maintaining the state of immune response whereas CD-86 plays a role in maintaining immune memory [40]. Also, CD86 plays an important role in the proliferation of lymphocytes that secrete Th2 cytokines like IL-4, IL-5 and IL-10 [41,42] while CD80 induction on antigen presenting cells mainly activates Th1 lymphocyte proliferation and cytokines like IL-2, IFN-γ and TNF-α produced by them [43,44]. PAF treatment increases the expression of both CD-80 as well as CD-86 which suggested that PAF may have the capacity to enhance the Th1 as well as Th2 immune response.
The present study evaluated mineral compound, pearl in ashed form [PAF], for its potential as oral immunomodulator. ICP-MS, atomic absorption spectroscopy, CHNS analysis and XRD analysis were used for characterization of PAF. Surface antigen markers (TLR-2/4 and CD-80/86) were studied by flow cytometry. At dose concentration of 25, 50, 100 and 500 μg/kg body wt., administrated orally for 10 days, TLR-2 expression on murine peritoneal macrophage increased while TLR-4 expression was reduced as compared to control. There was an increase in OVA and mitogen (Con-A) specific lymphocyte proliferation in OVA immunized mice. Also, level of both Th1 (IL-2/IFN-γ) and Th2 (IL-4/IL-10) cytokines, and level and titer of total IgG, IgG1, IgG2a and IgG2b of OVA immunized mice significantly increased. The level of Inflammatory cytokines (IL-1β and TNF-α) did not increase significantly. Enhancement in T and B cell immune responses may be possibly due to significantly enhanced expression of CD-80 and CD-86 co-stimulatory signals as observed using flow cytometry. Also, enhanced phagocytic activity and DTH response exhibit stimulatory effect of PAF on innate and cell mediated immune response. Histopathological analysis of liver, kidney and spleen and analysis of other toxicity parameters, such as effect on body weight, lymphoid organ weight and cellularity, revealed PAF to exhibit no toxic effects. PAF seems to be a promising balanced Th1 and Th2 directing immunomodulator, possibly activating TLR2 through TIR domain-containing adaptor inducing interferon β (TRIF)-dependent pathway that leads to T-cell activation and promotes effective immune responses and may find useful application clinically.
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In this study we observed no significant difference in the frequency of CD14+ cells expressing CD80 or CD86 between infected and uninfected asthmatics. It has been demonstrated that in atopic subjects, CD86 expression is up-regulated on B cells [22] and in alveolar macrophages after allergen challenge [23]. In chronic helminth infections the expression of CD86 is also up-regulated [24].
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To investigate the effects of segmental allergen challenge on the concentration of soluble CD86 (sCD86) in BAL fluids in patients with allergic asthma.
BAL fluid and peripheral blood were collected at baseline, 24 h after segmental saline solution or allergen challenge by fiberoptic bronchoscopy and venepuncture, respectively, from 10 patients with allergic asthma. Total and differential cell counts in BAL fluid were performed, and sCD86 levels in both BAL fluid and serum were measured by enzyme-linked immunosorbent assay.
In allergic asthmatics, there was no significant increase in BAL sCD86 concentrations after saline solution challenge (median, 2.0 IU/L; 25th to 75th percentiles, 0 to 3.4) compared with baseline control subjects (median, 1.2 IU/L; 25th to 75th percentiles, 0 to 3.6 IU/mL; p = 0.735); however, sCD86 concentrations were significantly elevated after allergen challenge (median, 8.1 IU/L; 25th to 75th percentiles, 4.4 to 17.0 IU/mL; p < 0.001). The concentrations of sCD86 in BAL fluid after allergen challenge exceeded levels that could be accounted for passive transudation from the circulation, based on the magnitude of increases in BAL albumin concentrations.
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^☆: From ^athe Department of Pediatrics, The National Jewish Medical and Research Center and ^bthe Department of Pediatrics, University of Colorado Health Sciences Center, Denver.

^☆☆: Supported by Public Health Services Research grants nos. HL36577, AR41256, and HL37260; General Clinical Research Center Grant no. 5 MO1 RR00051 from the Division of Research Resources; and an Asthma Research Center Grant from the American Lung Association and the University of Colorado Cancer Center.

^★: Reprint requests: Donald Y. M. Leung, MD, PhD, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206.

^★★: 1/1/85981

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Upregulation of B7.2, but not B7.1, on B cells from patients with allergic asthma☆,☆☆,★,★★

Abstract

Section snippets

Reagents

Increased expression of B7.2 on B cells of atopic patients with asthma

DISCUSSION

Cell

Immunity

J Allergy Clin Immunol

Blood

Cell

Immunity

Adv Immunol

CD28/B7 system of T cell costimulation

Annu Rev Immunol

Costimulatory B7 molecules in the pathogenesis of infectious and autoimmune diseases

N Engl J Med

Surface proteins involved in T cell costimulation

J Leukoc Biol

Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma

N Engl J Med

Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production

J Exp Med

IgE-receptor bearing lymphocytes in allergic and nonallergic children

Pediatr Res

Low-affinity IgE receptor (CD23) function on mouse B cells; role in IgE-dependent antigen focusing

Proc Natl Acad Sci USA

CD21 is a ligand for CD23 and regulates IgE production

Nature

The murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T cell receptor/CD3 complex

Proc Natl Acad Sci USA

Predominant T_H2-like bronchoalveolar T-lymphocyte population in atopic asthma