Stimulatory and Inhibitory Effects of Cyclic AMP on Lymphocytes from Atopic Children

Strannegård²

1984

Self Cite

The viability of cultured peripheral blood mononuclear cells (MNC) from atopic children was found to be subnormal. After 3 days of culture, less than 5% of cells from nonatopic children had died as judged by trypan blue exclusion tests, whereas more than 4 times as many dead cells were observed in cultures of cells from atopies with high IgE levels (> 400 units/ml). MNC from atopies with low or moderately increased IgE levels did not display any significantly decreased viability. Low cell viability was observed primarily in cultures from patients with atopic dermatitis, but also in cases with respiratory allergy with high IgE levels but without concomitant atopic dermatitis, there was a decreased viability. There was no evidence that low cell viability was causally related to occurrence of cytotoxic serum factors. Results of experiments where dibutyryl cyclic AMP or theophylline was included in the cultures suggested that a possible explanation for the decreased viability might be altered sensitivity of the cells to inactivation by cyclic AMP promoting substances.

Section: Effect Of Theophylline and Dibuturyl Cyclic Amp On Cell Viabmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Viability of Cultured Peripheral Blood Mononuclear Cells from Atopic Individuals

Strannegård²

1984

Self Cite

“…There is a re markable similarity, however, between dose-response curves obtained in mitogen-induced lymphocyte pro liferation assays [Strannegard and Strannegard, 1979] and the presently described IgE system. Therefore it is possible that the stimulatory effect of cAMP-elevating agents on IgE synthesis reflects a general capacity of these agents to stimulate lymphocyte-mediated re sponses.…”

Section: Discussionmentioning

confidence: 69%

“…Both inhibitory and enhancing effects have been ascribed to this substance [reviewed by Strom et al, 1977], Mitogen-induced lymphocyte proliferation is inhibited by high concentrations (> 10'5 M) of cAMP whereas low concentrations have been found to stim ulate proliferation in humans [Strannegard and Strannegard, 1979]. There is no clear explanation for this dual effect of cAMP, but it has been suggested that certain suppressor cells are unusually sensitive to inactivation by cAMP and, therefore, preferential in activation of such cells might lead to enhancement of immune responses [Katz and Fauci, 1978;Strannegard and Strannegard, 1978].…”

Section: Introductionmentioning

confidence: 99%

Effect of Cyclic AMP-Elevating Agents on Human Spontaneous IgE Synthesis in vitro

Strannegård²

1984

The cyclic AMP (cAMP)-elevating substances dibutyryl-cAMP (dbcAMP), isoproteronol and theophylline were found to suppress the spontaneous in vitro IgE synthesis of peripheral blood mononuclear cells (MNC) from patients with atopic dermatitis, when added at high concentrations (10^––³–10^––4M) to the IgE-producing cell cultures. In contrast, low concentrations of the substances (10^––8–10^––12M) significantly enhanced IgE production. This enhancement was probably due to effects of cAMP on T cells since pretreatment of allogeneic MNC or T cells with dbcAMP abrogated their suppressive effect or resulted in enhancement of IgE synthesis in coculture experiments. Likewise, pretreated T cells from atopies stimulated the IgE production of autologous B cells more than did untreated T cells. These findings may possibly have bearing on the pathogen-esis of the atopic diseases, which are associated with abnormalities of the cyclic nucleotide metabolism.

“…Kümmeret al [16] have recently shown that transition of T4+ to T8* cells and Tu to Ty cells is positively influenced by adeno sine, and prostaglandin E2 appears to induce expres sion of the FclgG receptor on human T cells [19], Since these substances increase intracellular cyclic AMP levels and the response to several cyclic AMPactive agonists is decreased in AD [28], it is possible that the observed imbalance between T lymphocyte subsets is secondary to a basic defect in cyclic AMP induction or degradation. Another possible explana tion for a suppressor cell deficiency in atopy would be that certain suppressor cells are sensitive to cyclic AMP-mediated inactivation [20,33] and T lympho cytes from atopies appear to be more sensitive than cells from nonatopics to such inactivation [35]. Dis tinguishing between these possibilities will have to await further characterization of suppressor cells that regulate IgE synthesis.…”

Section: Discussionmentioning

confidence: 99%

FcIgG Receptor-Bearing Lymphocytes and Monoclonal Antibody-Defined T Cell Subsets in Atopic Dermatitis: Effect of Treatment with Thymopoietin Pentapeptide (TP-5)

Strannegård

Kang

et al. 1982

Lymphocyte subpopulations were determined in the blood of patients with atopic dermatitis (AD) before and after treatment with the thymopoietin pentapeptide TP-5. The relative and absolute numbers of lymphocytes bearing suppressor/cytotoxic cell markers (FcIgG⁺E⁺ and T8⁺ cells) were significantly decreased in the untreated patients and the T4⁺/T8⁺ cell ratio was increased, indicating an imbalance between lymphocyte subpopulations in AD. Patients who had been treated for 6 weeks with TP-5 displayed no significant abnormality of any of the lymphocyte subsets studied and comparison of pre- and posttreatment values revealed that there was a statistically significant increase in T8⁺ cell numbers, that by contrast did not take place in placebo-treated AD patients. The treatment had no demonstrable effect on IgE serum levels or on the spontaneous in vitro production of IgE by cultured lymphocytes from the patients.