Esa Soppi

Cell-mediated immunity in Darier's disease: effect of systemic retinoid therapy.

In five patients with Dariers disease, lymphocyte subpopulations, lymphocyte responsiveness to phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and purified protein derivative of tuberculin (PPD), leukocyte migration inhibitory factor (LMIF) production and suppressor cell activities were studied before and during oral etretinate treatment. Pre‐therapy investigations of cell‐mediated immunity showed no severe immunological dysfunction, although high responses to supra‐optimal Con A concentrations suggested abnormalities in immunoregulatory lymphocyte subpopulations. In addition, two patients showed enhanced LMIF production upon stimulation with Con A, PWM and PPD. Retinoid therapy decreased the number of peripheral blood total leukocytes, lymphocytes and T‐cells, normalized the LMIF production, and decreased the lymphocyte responses to mitogens. Furthermore, the dose‐response curve to Con A changed toward normal and the suppressor cell activity regulating Con A responses tended to increase.

Effects of indomethacin on lymphocyte proliferation, suppressor cell function, and leukocyte migration inhibitory factor (LMIF) production

The in vitro effect of indomethacin (IND) on PHA- and Con-A-induced immune responses was studied. The results showed that the enhancement of both PHA and Con A responses by IND does not significantly depend on the concentrations of mitogens or IND. A significant negative correlation was found between the initial PHA response and augmentation index, whereas there was a positive correlation between the initial Con A response and the enhancement of the Con A responses. Indomethacin significantly increased the Con-A-induced suppressor cell activity and PHA-induced leukocyte migration inhibitory factor production (LMIF), whereas the effects on the PHA-induced suppressor cell activity and Con-A-induced LMIF production were not significant. The findings indicate the indomethacin has a dual effect on PHA- and Con-A-induced immune responses probably reflecting intrinsic differences among T cells, for example, distinct lymphokines produced by different T-cell subpopulations.

Differential in vitro effects of etretinate and retinoic acid on the PHA and Con a induced lymphocyte transformation, suppressor cell induction and leukocyte migration inhibitory factor (LMIF) production

The in vitro influence of two retinoids, etretinate and retinoic acid, on the human lymphocyte transformation, on the induction of suppressor cells and on leukocyte migration inhibitory factor (LMIF) production were investigated. Nontoxic concentration of retinoic acid increased significantly the PHA response to suboptimal mitogen concentrations, but had no effect on the Con A response; it also abolished the PHA induced LMIF production. In corresponding assays etretinate was without effect. Etretinate augmented the PHA induced suppressor cell activity, while retinoic acid was ineffective. No effect was observed on Con A induced suppressor cells by either retinoid. The findings extend the information about the immunomodulatory effects of retinoids and demonstrate that retinoic acid and etretinate have different effects on PHA and Con A induced immune responses. The mode of action of retinoids is discussed.

PUVA treatment in chromium hypersensitivity: effect on skin reactivity and lymphocyte functions.

SummaryTwo male patients with longstanding contact sensitivity to chromium were treated with PUVA. One patient, suffering from concomitant photosensitivity, reacted very favorably; his skin lesions cleared and light tolerance increased. This was paralleled by a decrease in the photopatch test reactivity and by the extinction of the patch-test reactivity on PUVA-exposed (pigmented) skin. Patch and photopatch tests on PUVA-shielded skin showed no decrease in skin test reactivity. PUVA-treatment caused a decrease in the number of rosette-forming T cells and an increase in lymphocyte stimulation in both patients. In one patient, abnormally high PHA-induced suppressor cell activities were recorded prior to treatment; after PUVA therapy the values were back to normal. In both patients, the PPD-induced suppressor cell activity of PWM response was clearly increased by PUVA-therapy. Other suppressor cell functions were not much affected. It is concluded that while PUVA-therapy may produce some systemic immunological effects, its abating effect on contact sensitivity and photosensitivity is mainly mediated through local mechanisms in the skin.ZusammenfassungZwei Patienten mit lang bestehender Kontaktempfindlichkeit auf Chrom wurden mit PUVA behandelt. Ein Patient, der gleichzeitig eine Photosensibilisierung aufweist, reagierte sehr günstig. Seine Haut besserte sich und die Lichttoleranz erhöhte sich. Dies war von einer Abnahme der Phototestreaktivität begleitet, die auf der PUVA-exponierten Haut (pigmentiert) graduiert werden konnte. Der Läppchentest und der Phototest auf der für PUVA geschützten Haut zeigte keine Verminderung der Hauttestreaktivität. PUVA-Behandlung verursachte eine Abnahme der Zahl der Rosettenbildenden T-Zellen und eine Intensivierung der Lymphocytenstimulation in beiden Patienten. Bei dem einen Patienten, der eine außergewöhnlich hohe PHA-induzierte Suppressor-Zellaktivität vor der Behandlung zeigte, wurden durch die Behandlung die Werte zur Norm zurückgebildet. Bei beiden Patienten wurde die PPD-induzierte Suppressor-Zellaktivität auf PWM deutlich durch PUVA-Therapie vermehrt. Andere Suppressor-Zellfunktionen waren nicht beeinträchtigt. Es wurde der Schluß gezogen, daß während der PUVA-Therapie wohl einige systemische immunologische Effekte auftreten können, der abschwächende Effekt auf die Kontaktsensibilisierung und Photosensibilisierung aber vornehmlich durch lokale Vorgänge in der Haut hervorgerufen werden.

Effect of thymosin on PHA and Con A responses by fetal lamb lymphocytes.

Abstract The effects of thymosin fraction 5 on the mitogen responses of fetal lamb lymphocytes in serum-free cultures were studied. The cells from liver, thymus, spleen, and bone marrow of 12 fetal lambs of four different ewes at 48–98 days of gestation (total gestation is 150 days) were used. Cells from the liver, bone marrow, and spleen were separated by Ficoll-Isopaque density-gradient centrifugation. At 48 to 68 days of gestation, fetal liver cells had only a slight capacity to respond to PHA and Con A mitogens; however, these responses could be induced by thymosin. Later on, when the fetal lymphocytes including those from liver, thymus, spleen, and bone marrow started to respond to mitogens (from Day 78 onward), the effect of thymosin became negligible.

Postnatal development of mitogen responsiveness of guinea pig lymphocytes

Abstract Guinea pigs are believed to be immunologically mature at birth. There is, however, little data available to support this concept. In this study, the postnatal development of the lymphocyte responsiveness to Tand B-cell mitogens in the guinea pig was investigated. The results show that guinea pigs are not immunologically mature at birth as to the mitogenic responses of blood lymphocytes. The constant level of PHA response in the blood is achieved from the age of 1 to 2 months and that of Con A at the age of 3–6 months. Furthermore, the results support the concept that the emigration of thymocytes occurs also during postnatal life. The emigration of PHA-responsive thymic cells seems to precede and be greater than that of Con A-responsive cells. These findings provide important clues for studies on the ontogenetic development of cell-mediated immunity.

Effect of levamisole on the maturation of guinea pig thymocytes.

Abstract Alkaline phosphatase (AP) is a useful cell membrane marker of guinea pig thymocytes. Thymocytes with various AP activities represent different maturation stages of these cells. In this work, levamisole was found to effectively inhibit the AP activity in homogenates of thymus and thymocytes, but did not modify the AP activity of viable thymocytes. It significantly increased the number of E rosettes binding nine or more erythrocytes, but induced no change in the total number of rosette-forming thymocytes. It significantly augmented the PHA, but not the Con A, response of unfractionated thymocytes, while it had no effect on the mitogenic responses of the two subpopulations of thymocytes. The results support the concept that levamisole acts to mature a part of thymocytes as a thymomimetic compound without affecting the AP activity in the thymocyte cell membrane.

Immune functions in inflammatory bowel and coeliac diseases

Different immune functions of 10 patients with glutein‐sensitive enteropathy (GSE), 9 with Crohns disease (CD), 11 with ulcerative colitis (UC) and 13 healthy controls were characterized. The numbers of suppressor T cells in GSE were comparable to those of the controls; otherwise, the lymphocyte subpopulations were decreased in these bowel diseases. In the whole‐blood cultures, the lymphocyte proliferative responses to PHA were normal in the bowel diseases, but the responses to Con A were decreased in CD. In cultures with D‐penicillamine, the inhibition of the helper effect of CD patients was more pronounced in PHA‐stimulated cultures than in Con A‐stimulated cultures. The total Ig and IgA production did not markedly differ among the groups. PWM‐induced IgM secretion was significantly decreased in GSE, CD and UC, and IgG secretion in CD and UC, as compared to controls. In GSE, an increased Con A inducible suppressor cell activity was observed in the IgM production. Altogether, no clear‐cut immunological imbalance was detected in any of the bowel diseases; this in agreement with previous works. However, there are some differences in the regulatory cell balance among the patients with GSE, CD and UC. The determination of lymphocyte proliferative responses to PHA and Con A together with D‐penicillamine seems to provide a new immunological criterium for distinguishing between Chrohns disease and ulcerative colitis.

Ontogeny of phytohemagglutinin and concanavalin A responses in the human fetus: Effect of thymosin

Abstract Ontogenic development of phytohemagglutinin (PHA) and concanavalin A (Con A) responses of cells from 22 human fetuses at 6–23 weeks of gestation was studied. The results show that PHA responses appear earlier and stronger than Con A responses during the early fetal period. Similar to the findings reported for the mouse, sheep, and guinea pig, the mitogen responsive cells were first found in the thymus and thereafter in the spleen. The effect of thymosin on human fetal cells was variable, since thymocytes and spleen cells of only 2 out of 13 fetuses studied were susceptible to low concentrations (0.001–0.1 μg/ml) of thymosin. Higher concentrations (1.0–200 μg/ml) increased 5[125I]iodo-2′-deoxyuridine (125IUdR) uptake of PHA- and Con A-stimulated cells in few fetuses. In the fetal liver and bone marrow, thymosin-induced increase of 125IUdR uptake was observed both in unstimulated and mitogen-stimulated cells, however, without any significant effect on stimulation indices.

Effect of thymosin on the mitogenic responses of guinea pig thymocytes with different maturation stages.

Abstract Unfractionated guinea pig thymocytes were preincubated for two hours with 14 different concentrations of thymosin fraction 5 and thereafter the thymocytes were stimulated with mitogens. Three concentrations (0.05, 10 and 200 μg/ml) of thymosin significantly increased the PHA response of thymocytes; one concentration (0.05 μg/ml) significantly increased the Con A response. The results were not due to thymosin-induced changes in the PHA or Con A dose-response curves. Thymosin fraction 5 was also tested on two subpopulations of thymocytes at different stages of maturation. Thymosin did not increase PHA or Con A responses in the immature subpopulation. In contrast, it induced a significant inhibition of proliferation in these cells. Thymosin concentrations of 0.05 and 10 μg/ml significantly increased the PHA and Con A responses of the more mature subpopulation of thymocytes. The results support the concept that thymosin fraction 5 at concentrations of 0.05 and 10 μg/ml convert thymocytes into more mature PHA and Con A reactive cells. Higher concentration of thymosin (200 μg/ml) probably induces maturation of thymocytes to PHA reactive cells. These findings suggest that various concentrations of thymosin act to mature thymocytes at different stages of maturation; higher concentrations of thymosin are required to affect immature thymocytes than are required to affect more mature cells.