Biomedical subjects

K Vandenborre

Publications and source records attributed to K Vandenborre.

5 recordsLinked to original sources

PubMed1999

Interaction of CTLA-4 (CD152) with CD80 or CD86 inhibits human T-cell activation.

Occupancy of CTLA-4 (cytotoxic T-lymphocyte antigen-4 or CD152) negatively regulates the activation of mouse T lymphocytes, as indicated by the fate of CTLA-4-deficient mice, by the impact of anti-CTLA-4 monoclonal antibodies (mAbs) on mouse T-cell activation in vitro and by the impact of CTLA-4 blockade on the course of experimental tumoral, autoimmune, alloimmune or infectious disease in this animal. The function of human CTLA-4, however, remains less clear. The expression and function of human CTLA-4 were further explored. CTLA-4 was expressed under mitogenic conditions only, its expression being, at least partially, dependent on the secretion of interleukin-2. Memory T cells expressed CTLA-4 with faster kinetics than naive T cells. The functional role of human CTLA-4 was assessed utilizing a panel of four anti-CTLA-4 mAbs that blocked the interaction between CTLA-4 and its ligands. These mAbs, in immobilized form, profoundly inhibited the activation of T cells by immobilized anti-CD3 mAb in the absence of anti-CD28 mAb, but co-stimulated T-cell activation in the presence of anti-CD28 mAb. Finally, and importantly, blockade of the interaction of CTLA-4 with its ligands using soluble anti-CTLA-4 mAbs, in intact form or as Fab fragments, enhanced T-cell activation in several polyclonal or alloantigen-specific CD80- or CD80/CD86-dependent assays, as measured by cytokine production, cellular proliferation or cytotoxic responses. It is concluded that interaction of CTLA-4 with its functional ligands, CD80 or CD86, can down-regulate human T-cell responses, probably by intracellular signalling events and independent of CD28 occupancy.

Abatacept↗

PubMed1998

Human CTLA-4 is expressed in situ on T lymphocytes in germinal centers, in cutaneous graft-versus-host disease, and in Hodgkin's disease.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152) is a molecule expressed on in vitro activated T cells. CTLA-4 shares important sequence homology with CD28 and binds to the same ligands, CD80 (B7-1) and CD86 (B7-2). CTLA-4 probably functions as a negative regulator of T lymphocyte activation in the mouse, although this remains to be proven for human T lymphocytes. We have developed new monoclonal antibodies against human CTLA-4 and have investigated the in situ expression of CTLA-4 in a wide variety of normal and pathological human tissues expressing CD80 and CD86. As revealed in this study, CTLA-4 is expressed on thymocytes in thymic medulla, on a subset of CD4+ T lymphocytes in germinal centers of follicular hyperplasia, on T cells, mainly CD8+, infiltrating skin affected by graft-versus-host disease, and on T cells, mainly CD4+, infiltrating Hodgkin's disease lesions. In immunoelectron microscopy, CTLA-4 was found on the plasma membrane as well as in the hyaloplasm and cytoplasmic vesicles, in agreement with its pattern of expression on in vitro activated T cells. Interestingly, no or at most scarce expression of CTLA-4 was found in granulomatous lymph nodes, T-cell-mediated inflammatory diseases, or non-Hodgkin's lymphomas, regardless of their expression of CD80 or CD86. Thus, expression of CTLA-4 appears to be induced in selective pathological conditions in vivo. The pathways leading to selective induction of CTLA-4 and its role in the pathophysiology of these conditions need to be further investigated.

Abatacept↗

PubMed1996

[Squamous esophageal papillomas].

In three patients, two women of 37 and 58 and a man of 68 years, a papillomatous lesion was incidentally detected in the distal part of the oesophagus. Microscopically a squamous papilloma was seen with parakeratosis and in two patients poikilocytosis, indicating an infection with human papilloma virus (HPV). The lesions were removed endoscopically, in one patient with laser photocoagulation. Squamous papillomas of the oesophagus are benign tumours with a very low incidence. The pathogenesis still remains unclear. Some authors suggest local irritation as a possible mechanism. On the other hand there is growing evidence of an aetiological role of HPV. In several studies the presence of viral antigen or DNA has been demonstrated. These papillomas may undergo malignant transformation, which means that they are best removed preventively.

Adult↗

PubMed1993

VACTERL with hydrocephalus. A distinct entity with a variable spectrum of multiple congenital anomalies.

In this report we describe the experience and follow-up data in 4 patients presenting the "VACTERL-hydrocephaly association". A review of the literature and the present data show that the inheritance pattern of this association is not clear at the present time and that data on the long-term prognosis are scarse.

Abnormalities, Multiple↗

PubMedDate not supplied

Lymphocytic gastritis. Clinical and endoscopic presentation and long-term follow-up.

Lymphocytic gastritis is a histopathological entity corresponding with diffuse varioliform gastritis but also with other gastroscopic findings. Eighteen patients were followed over a mean period of 25 months. The symptoms, the endoscopic and histopathological abnormalities remained unchanged in the majority of the cases. Conventional peptic ulcer therapy failed to control symptoms or to normalize endoscopic alterations. Helicobacter pylori did not seem to play a role in the pathophysiology. Lymphocytic duodenitis was found in four patients. The relationship between lymphocytic gastritis, Ménétrier's disease and coeliac disease has further to be elucidated.

Adult↗