Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study.

Forty patients with Graves' ophthalmopathy stages III-V were divided into two groups in a random manner according to their year of birth. Group I received prednisone in decreasing dosage. Group II received prednisone at a comparable dosage and ciclosporin. Steroids were discontinued after 10 weeks in the two groups. In the patients of group II, ciclosporin was continued over 12 months. The therapeutic effect was assessed by an activity score based on subjective and objective symptoms (computerized tomography and sonography of the orbit, Hertel values, clinical findings). All signs of endocrine ophthalmopathy improved significantly in both groups (P less than 0.01 in group I; P less than 0.0…

T cell receptor gene rearrangements of T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis (PBC): Oligoclonality of PBC-derived T cell clones

Immunological events are involved in the pathophysiology of chronic active hepatitis as indicated from the accumulation of T lymphocytes at the site of tissue damage. We generated T cell clones from liver biopsies of 3 patients with chronic active hepatitis B and 2 patients with primary biliary cirrhosis. These T cell clones (n = 84) were analyzed by means of T cell receptor (TcR) beta gene rearrangements to determine whether the infiltrate consists of a polyclonal or oligoclonal T cell population. The vast majority (62 of 64) of T cell clones from three different patients with chronic active hepatitis B showed no identical rearrangements of the TcR beta chain genes. In marked contrast, in …

Hepatitis-B-Impfung bei Dialysepatienten*

Sekundärer Immundefekt bei Niereninsuffizienz am Beispiel der Hepatitis B-Impfung

In dialysis patients the immune response to hepatitis B-vaccination is greatly impaired. In vitro the non-responders show a failure of the monocytes to support the process of primary T-cell activation. This defect results in a lack of interleukin 2-production and an enhanced sensitivity of the interleukin-2 receptor system. Addition of low doses of interleukin-2 fully reconstitutes the deficient immune response in vitro. Furthermore, the local application of low dose interleukin-2 during a standard vaccination with 40 µg hepatitis B-vaccine normalizes the non-responder state in vivo.

LOW-DOSE INTERLEUKIN-2 INDUCES SYSTEMIC IMMUNE RESPONSES AGAINST HBsAg IN IMMUNODEFICIENT NON-RESPONDERS TO HEPATITIS B VACCINATION

Abstract A metabolic monocyte defect appears to correlate with non-responsiveness to hepatitis B vaccine in many patients on haemodialysis. This defect prevents production of interleukin-2 during T-cell activation after antigen contact. Receptors for interleukin-2 are, however, expressed in greater numbers than in healthy subjects or uraemic responders to hepatitis B vaccination. In this study, ten uraemic patients, previous non-responders to vaccination against hepatitis B, were revaccinated with the same vaccine combined with one intramuscular injection (2·5 × 10 5 U) of natural human interleukin-2. Systemic production of antibodies against hepatitis B surface antigen was initiated in tho…

Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand.

Activation of resting T lymphocytes is initiated by the interaction of cell-surface receptors with their corresponding ligands. In addition to activation through the CD3 (T3)-Ti antigen-receptor complex1, recent experiments have demonstrated induction of T-cell proliferation through the CD2 (T11) molecule2–4, traditionally known as the erythrocyte(E)-receptor, through which T cells can bind red blood cells (RBC)5–7. This 'alternative pathway' of T-cell activation2 was observed in vitro in response to combinations of anti-CD2 monoclonal antibodies (mAbs) that bind to distinct epitopes of CD2, such as mAbs against T112 plus T113 (ref. 2). The physiological importance of this activation pathwa…

Lymphocytes from hepatic inflammatory infiltrate kill rat hepatocytes in primary culture

In the last few years it has become possible in the liver to isolate lymphocytes from inflammatory infiltrates and to culture them in vitro. Most of the lymphocyte clones obtained are CD 8 + cytotoxic cells, but interactions between these lymphocytes and hepatocytes in primary culture have not been analysed previously. In this study, cloned human T lymphocytes from liver biopsies and from the peripheral blood of patients with chronic hepatitis B or primary biliary cirrhosis, after phenotypical and functional characterization into CD 8+ or CD 4+ cytotoxic lymphocytes, were activated in an antigen-independent fashion by adding either anti CD 3 or anti CD 2/R-3 monoclonal antibodies to the cel…

Expression of Ia-antigens on guinea pig Kupffer cells

Summary The expression of the Ia-antigen on guinea pig Kupffer cells was studied employing two monoclonal antibodies against two different determinants of the Ia-molecule. The study was performed in situ on liver sections and on isolated highly purified Kupffer cells kept in culture up to 6 days. The influence of guinea pig hepatocyte culture supernatant and of supernatants of phytohemoagglutinin (PHA)-stimulated human peripheral blood lymphocytes (PBL) on the Ia expression was measured. Immunofluorescence staining of cryostat sections revealed that the monoclonal antibodies used are able to detect Ia-antigens on liver macrophages in situ. The in vitro studies strongly suggest that all Kupf…

Definition of discrete signals involved in human T-cell activation

Abstract Mitogenic activities of monoclonal antibodies directed at denned receptor structures expressed on the surface of mature human T lymphocytes were employed to study, in detail, signals involved in primary T-cell activation. Based on differential requirements for stimulation, two discrete pathways of human T-cell activation can be defined: the antigen-induced mode of activation initiated through the Ti-T3 antigen-receptor complex and an alternative pathway which can be triggered by monoclonal antibodies directed at the T11 glycoprotein. Perhaps more importantly, the approach taken here allows the definition of stable intermediate cellular stages within the activation cascade and, thus…