T cells from human allergen-induced late asthmatic responses express IL-12 receptor beta 2 subunit mRNA and respond to IL-12 in vitro

TY - JOUR

T1 - T cells from human allergen-induced late asthmatic responses express IL-12 receptor beta 2 subunit mRNA and respond to IL-12 in vitro

AU - Varga, E M

AU - Wachholz, P

AU - Nouri-Aria, K T

AU - Verhoef, A

AU - Corrigan, C J

AU - Till, S J

AU - Durham, S R

PY - 2000/9/1

Y1 - 2000/9/1

N2 - IL-12 suppresses proallergic Th2-type cytokine production and induces Th1-type cytokine production by peripheral blood T cells from subjects with allergic disease. The objective of the present study was to examine the relevance of these findings to target organ T cell responses in human asthma. Bronchoalveolar lavage (BAL) and PBMC were collected from atopic asthmatics 24 h after fiberoptic allergen challenge of a segmental bronchus. BAL T cells and PBMC were cultured with allergen in the presence of recombinant IL-12 or IFN-gamma, and cytokines were measured in culture supernatants after 6 days. IL-5 production by BAL T cells and PBMC was inhibited by IL-12 and, to a lesser extent, by IFN-gamma. IL-12 also induced IFN-gamma production by BAL T cells and PBMC. The effects of IL-12 nor IFN-gamma on IL-5 production could not be reversed by neutralizing anti-IFN-gamma or anti-IL-12 mAbs, respectively. Thus, the effect of neither IL-12 nor IFN-gamma appeared to be mediated through induction of the other cytokine. In situ hybridization revealed that approximately one-third of BAL T cells expressed mRNA transcripts encoding the IL-12R beta 2 subunit following allergen challenge. Thus, human T cells obtained from BAL during asthmatic late responses, like T cells in the peripheral circulation, remain susceptible to immunomodulation by IL-12. These findings raise the possibility that IL-12 may hold therapeutic potential in allergic diseases such as asthma.

AB - IL-12 suppresses proallergic Th2-type cytokine production and induces Th1-type cytokine production by peripheral blood T cells from subjects with allergic disease. The objective of the present study was to examine the relevance of these findings to target organ T cell responses in human asthma. Bronchoalveolar lavage (BAL) and PBMC were collected from atopic asthmatics 24 h after fiberoptic allergen challenge of a segmental bronchus. BAL T cells and PBMC were cultured with allergen in the presence of recombinant IL-12 or IFN-gamma, and cytokines were measured in culture supernatants after 6 days. IL-5 production by BAL T cells and PBMC was inhibited by IL-12 and, to a lesser extent, by IFN-gamma. IL-12 also induced IFN-gamma production by BAL T cells and PBMC. The effects of IL-12 nor IFN-gamma on IL-5 production could not be reversed by neutralizing anti-IFN-gamma or anti-IL-12 mAbs, respectively. Thus, the effect of neither IL-12 nor IFN-gamma appeared to be mediated through induction of the other cytokine. In situ hybridization revealed that approximately one-third of BAL T cells expressed mRNA transcripts encoding the IL-12R beta 2 subunit following allergen challenge. Thus, human T cells obtained from BAL during asthmatic late responses, like T cells in the peripheral circulation, remain susceptible to immunomodulation by IL-12. These findings raise the possibility that IL-12 may hold therapeutic potential in allergic diseases such as asthma.

KW - Clone Cells

KW - Animals

KW - Interferon-gamma

KW - Interleukin-12

KW - Humans

KW - Asthma

KW - Pollen

KW - Receptors, Interleukin

KW - RNA, Messenger

KW - Antibodies, Monoclonal

KW - Epitopes, T-Lymphocyte

KW - Allergens

KW - Adult

KW - Bronchoalveolar Lavage Fluid

KW - Mites

KW - Interleukin-5

KW - Cytokines

KW - Receptors, Interleukin-12

KW - Time Factors

KW - Male

KW - Female

KW - T-Lymphocyte Subsets

M3 - Article

C2 - 10946321

SN - 1550-6606

VL - 165

SP - 2877

EP - 2885

JO - Journal of Immunology

JF - Journal of Immunology

IS - 5

ER -