Interleukin 2 induction of proliferation in resting T lymphocytes requires contact with monocytes

Resting human T cells are known to express significant numbers of intermediate but none or barely detectable low and high a affinity IL-2 receptors (IL-2R). IL-2 alone failed to induce proliferation in these cells, However, in presence of small proportion of autologous monocytes, as low as 22 pM, IL-2 induced high levels of proliferation in resting T cells. Introduction of a semi permeable between the two cell types or addition of an anti-CD 11b mAb inhibited such induction of proliferation by IL-2. Neither recombinant IL-1 por IL-1 containing cell-free extracts from activated monocytes substituted for intact monocytes. Autologous B cells failed to replace monocytes. Using antigen-specific cloned human T cells we have shown a lack of requirement for antigen. The proliferation was inhibited by anti-IL-2R alpha mAb. IL-2 appears to be unique since neither IL-4 nor IL-6, alone or in presence of monocytes, led to induction of proliferation in resting T cells. Combination of IL-2 and monocytes induced proliferation in all T cell subpopulations (CD4, CD8, CD45RA and CD45RO) and antigen-specific clones examined. It also induces mRNA and surface expression of IL-2R alpha, appearance of high affinity IL-2R and induction of proliferation in large proportions of T cells. As in humans, the IL-2 induction of proliferation in murine resting T cell required contact with syngeneic monocytes, suggesting that such a mechanism of cells activation is highly conserved.

Efectos contrapuestos de interleuquina-2 (IL-2) e interferón-y (IFN-y) sobre contractilidad cardíaca / Opposed efects of interleukin 2 (IL-2) and interferon-y (IFN-y) on cardiac contractility

Recientemente demostramos que la interleuquina 2 (IL-2) es capaz de incrementar la tensión contráctil de aurículas de rata asiladas a través de la activación de las fosfolipasas y de la proteína quinasa C. Los resultados de este estudio demuestran que la vía ß-adrenérgica está involucrada en la acción de IL-2 sobre el miocardio mientras que el IFNy interactúa con los colinoceptores muscarínicos. El efecto estimulante de IL-2 sobre la contractilidad se opone al efecto colinomimético inhibitorio del interferón y (IFNy). La preincubación de las aurículas con IL-2 suprime la respuesta al IFNy y viceversa. La proteína quinasa C es también necesaria para que ocurra la interferencia IL-2-IFNy. Los resultados de este estudio sugieren que, durante un proceso inflamatorio en el corazón, el balance local de ambas linfoquinas puede determinar cambios en la respuesta del tejido hacia agonistas propios del sistema nervioso autónomo y hacia las citoquinas que imitan los efectos de dichos neurotransmisores.

Treatment of patients with hemophilia A and inhibitors to factor FVIII with cimetidine

In this study, cimetidine was used to treat patients with hemophilia A and inhibitors to factor VIII who presented with acute hemorrhages (Group A) and those without hemorrahges (Group B). The dose of cimetidine was 15 mg/kg/day. Group A consisted of five patients with inhibitors between 156 and > 10,000 Bethesda Units (BU), all with serious hemorrhagic problems. The control of hemorrhaging was effective in 100 per cent of these patients, although inhibitor levels remained high (25-380 BU). Group B consisted of seven patients who did not have hemorrhages, whose inhibitor levels were 41-358 BU. Five of these patients no longer had anamnestic responses to Factor VIII after several months of treatment with cimetidine. No difference in the response to cimetidine was seen between HIV positive and HIV negative patients. The results suggest that cimetidine is useful to suppress inhibitores to Factor VIII in patients with hemophilia A

Interleucina-2: una terapia alternativa en cáncer / Interleukin-2: an alternative therapy for cancer

Recientemente, se ha demostrado que la manifestación de inmunidad antitumoral resulta de las interacciones entre varias poblaciones celulares del sistema inmune. La inmunoterapia con interleucina-2 (IL-2) y células destructoras de linfocinas activadas generadas por linfocitos análogos ha producido regresiones significativas en tumore de pacientes con cáncer avanzado. El efecto mitogénico de la IL-2 en linfocitos T citolíticos de tumores-reactivos (CTL), destructores naturales y LAK puede incrementar el potencial de defensa en la expansión de tumores. A diferencia del tratamiento sistémico, la administración de IL-2 en la vecindad del tumor puede ofrecer ciertas ventajas, tales como: uso de dosis bajas y menos anticuerpos anti IL-2 y proveer un cambio de confrontación mucho mejor con inhibidores IL-2 y mecanismos de retroalimentación, los cuales podrán limitar sustancialmente los posibles efectos terapéuticos de la IL-2 en pacientes con tumores

Patients with hepatic cirrhosis: altered lymphocyte response to mitogens and its relation with plasmatic zinc, albumin and transferrin

Patients with alchoholic hepatic cirrhosis have a higher predisposition to acquiring infections than healthy individuals, suggesting an alteration in the immune system. They also exhibit an important decrease in certain plasmatic constituents such as zinc, albumin, and transferrin which are involved in the normal immune response. The blastoid transformation of lymphocites stimulated in vitro with phytohemaglutinin M and P in patients with alcoholic hepatic cirrhosis was studied and the results were correlated with the plasmatic constitutents aforementioned. The rate of blastoid transformation was significantly lower (p<.001) in these patients when compared to the control group, but did not correlate directly with the concentration of zinc, albumin, transferrin or circulating globulins. Patients' plasma significantly inhibited the response of normal cells to stimulation with phytohemaglutinin and Concanavalin A; nevertheless, the blastoid transformation of lymphocytes in these patients was not restored to normal levels when incubated with control plasma

Prostaglandin E2 inhibits proliferation but not interleukin-2 production by phorbol ester plus calcium ionophore-activated murine T cell clones

We have investigated the effect of prostaglandin E2 (PGE2) on the T lymphocyte activation pathway. 2. At physiologically attainable concentrations (-0.1 micronM), PGE2 effectively inhibited the proliferation of murine antigen0specific "helper" T cell clones stimulated either with specific antigen in the presence of macrophages or with phorbol ester plus calcium ionophore A23187. The inhibition was not reversed by the addition of exogenous Interleukin 2(IL-2) in either case. 3. PGE treatment at the same concentrations did not inhibit IL-2 production by phorbol ester plus calcium ionophore-stimulated T cell clones as assayed by CTLL proliferation. 4. These results suggest that the major target (or targets) of PGE) inhibition directly on T cells lies in the IL-2 signal transduction pathway rather than in the early activation events leading to T cell activation

Interleukin-2 induced activation of natural killer cells in rats and mice: a comparative study.

Effects of interleukin-2 (IL-2) on the natural killer (NK) activities of BALB/c mouse and Wistar rat spleen cells were compared. While mouse spleen cells cultured alone rapidly lost NK activity, co-culture with IL-2 resulted in a marked enhancement of NK activity. In contrast, the levels of NK activity of rat spleen cells cultured alone increased and remained high for 3 days and declined thereafter. Addition of human recombinant IL-2 or purified rat IL-2 did not influence the NK levels in rat spleen cell bulk cultures. Both IL-2 preparations were however biologically active as shown by their capacities to induced proliferation in rat spleen cells. Rat spleen cells suppressed the IL-2 activation of mouse spleen cells in a dose dependent manner, indicating a suppressor influence generated by rat spleen cells. Culture supernatants of rat spleen cells cultured with or without IL-2 for 3 or 5 days could also suppress the mouse spleen NK activation in response to IL-2. The suppressor activity could be concentrated on a 5K MW cut-off Amicon filter indicating that the molecular weight of the factor is more than 5000. These results indicate that a suppressor of IL-2 induced NK activation of mouse spleen cells is released by cultured rat spleen cells.

Regulación de la respuesta inmune mediada por interacciones celulares: su relación con la inmunidad anti-tumoral / Regulation of the immune responce mediated by cellular interactions: its relation to anti-tumor immunity

Se describen los posibles mecanismos de regulación de la respuesta inmune en el ratón, fundamentalmente los mediados por interacciones celulares. Los macrófagos presentan el antígeno a células T que se caracterizan por poseer el marcador de superficie Lyt 1, y reconocen a antígenos del complejo mayor de histocompatibilidad de clase II en al superficie de la célula presentadora del antígeno. Estos macrófagos liberan un factor solubre, 1a IL-1, que activa a las células Lyt 1 las que como consecuencia de ello liberan otro factor soluble, 1a IL-2, que permite la proliferación y diferenciación celular. Las células T participan en la regulación de la respuesta inmune. Se sugiere que las células T colaboradoras estimulan una cascada de células T supresoras, cada una de ellas activando la próxima hasta llegar a la última que transmite una señal que reduce la actividad de las células colaboradoras. Por otra parte, las células supresoras hiperactivadas pueden reestimular a las células colaboradoras y así, por un mecanismo de feed-back se produciría la reactivación de las células B productoras de anticuerpos, de las células citotóxicas o de los macrófagos. También los macrófagos son esenciales en la regulación de la respuesta inmune ya que factores supresiones de las células que los producen a las células aceptoras. El sistema regulatorio también actuaría contra los antígenos específicos de tumor, los que pueden estar constituídos por antígenos que no se expresen al mismo tiempo, en la misma cantidad o en la misma localización que en las células normales