Heterogeneous Effects of Histamine on Proliferation of Lung- and Blood-derived T-Cell Clones from Healthy and Asthmatic Persons

Abstract

We have studied the effects of histamine on the proliferation and the intracellular cyclic adenosine monophosphate (cAMP) levels of T-lymphocyte clones (TLC) generated from bronchoalveolar lavage fluid (BALF) or peripheral blood (PB) from healthy and asthmatic persons. TLC from either compartment and from both groups of donors were heterogeneous in their response to histamine. In BALF-derived TLC, three types of responses were observed: histamine inhibited, stimulated, or did not modulate the anti-CD3-induced proliferation. Histamine directly and dose dependently inhibited the anti-CD3-induced proliferation of six (two asthmatic) of 12 CD4+ BALF TLC, stimulated two BALF TLC (both nonasthmatic), and did not modulate the proliferation of four BALF TLC. The maximal inhibition was 70%, the maximal stimulation 200%, both at 10(-3) M histamine. The stimulation of proliferation was associated with increased interleukin-2 (IL-2) production, whereas the inhibition of proliferation was associated with decreased IL-2 production and downregulation of IL-2 receptor expression. The inhibitory effects could be partly reversed by H2-receptor antagonists and could be mimicked by an H2-receptor agonist. In contrast, the stimulatory effect was not reversed or mimicked by H1 or H2 antagonists or agonists. The majority of CD4+ TLC responded to histamine with a rise in the intracellular cAMP levels. A rise in cAMP, however, was often but not always associated with an inhibition of proliferation. In addition, stimulation of proliferation occurred in the absence of a rise in cAMP. We compared cAMP rises in panels of TLC obtained with high cloning efficiencies from the PB from a healthy person and from an asthmatic person.(ABSTRACT TRUNCATED AT 250 WORDS)

Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones

“…We deliberately chose to use a polyclonal stimulus that induced cytokine production but that was not associated with a strong proliferative response [17,29]. Indeed, the proliferation of TCC was very low following stimulation, and was not significantly influenced by the addition of histamine (not shown).…”

“…Histamine, in vitro, can stimulate alveolar macrophages to induce the release of b-glucuronidase [13], modify their phenotype [14] and activate bronchial epithelial cells [15] or eosinophils [16]. Histamine has been shown to reduce mitogen-induced T cell proliferation through its H 2 -receptor [17] and to inhibit the production of IL-2 and IFN-g by polyclonal agent-activated human peripheral blood mononuclear cells (PBMC) via H 2 -receptors [18]. Histamine appeared to act directly on T cells without accessory cell involvement [19].…”

Immunological mechanisms in specific immunotherapy

“…For T cells expressing H2R, it was shown that the histamine-induced cAMP pathway mobilizes protein kinase A (PKA), which negatively regulates T cell proliferation [87] by down-regulation of IL-2 and IFN-g [95,96] and by increased IL-10 production [97]. This could also be shown for T cells isolated from asthmatic patients [98]. We recently demonstrated that histamine enhances the responsiveness of Th2 cells to TGF-b in an H2R-dependent fashion, resulting in more efficient IL-4 suppression by TGF-b [99].…”

Products from human mast cell line cells enhance the production of interferon‐γ by CD8+ and CD4+ T cells

“…In mast‐cell deficient mice there is no influx of mononuclear cells into the mucosal tissue after local IgE‐mediated reactions 12 . Furthermore, mast‐cell mediators like histamine and prostaglandins, and mast‐cell derived cytokines modulate T‐cell proliferation and cytokine production 11,13–15 . Interestingly, mast cells derived from the nasal mucosa of patients with allergic rhinitis may release IL‐4 by which they may contribute to ongoing IgE production and allergic reactions 16 …”

“…We have earlier reported on the effects of the mast‐cell mediator histamine on human T cells. Histamine enhanced or inhibited T‐cell proliferation and cytokine production dependent on the cell type studied and conditions applied 14,15 . To obtain information on the influence of the whole spectrum of mast‐cell products on T cells we have extended our studies and used the human mast cell line HMC‐1 as a model for mast cells 17 .…”