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Y van Kooyk

Publications and source records attributed to Y van Kooyk.

61 records · Page 4Linked to original sources
PubMed1991

Activation of LFA-1 through a Ca2(+)-dependent epitope stimulates lymphocyte adhesion.

The leukocyte function-associated molecule-1 (LFA-1) plays a key role in cell adhesion processes between cells of the immune system. We investigated the mechanism that may regulate LFA-1-ligand interactions, which result in cell-cell adhesion. To this end we employed an intriguing anti-LFA-1 alpha mAb (NKI-L16), capable of inducing rather than inhibiting cell adhesion. Aggregation induced by NKI-L16 or Fab fragments thereof is not the result of signals transmitted through LFA-1. The antibody was found to recognize a unique Ca2(+)-dependent activation epitope of LFA-1, which is essentially absent on resting lymphocytes, but becomes induced upon in vitro culture. Expression of this epitope correlates well with the capacity of cells to rapidly aggregate upon stimulation by PMA or through the TCR/CD3 complex, indicating that expression of the NKI-L16 epitope is essential for LFA-1 to mediate adhesion. However, expression of the NKI-L16 epitope in itself is not sufficient for cell binding since cloned T lymphocytes express the NKI-L16 epitope constitutively at high levels, but do not aggregate spontaneously. Based on these observations we propose the existence of three distinct forms of LFA-1: (a) an inactive form, which does not, or only partially exposes the NKI-L16 epitope, found on resting cells; (b) an intermediate, NKI-L16+ form, expressed by mature or previously activated cells; and (c) an active (NKI-L16+) form of LFA-1, capable of high affinity ligand binding, obtained after specific triggering of a lymphocyte through the TCR/CD3 complex, by PMA, or by binding of NKI-L16 antibodies.

Antibodies, Monoclonal↗
PubMed1990

Triggering of the CD44 antigen on T lymphocytes promotes T cell adhesion through the LFA-1 pathway.

The CD44 molecule, a molecule which has been previously known as Hermes, Pgp-1, extracellular matrix receptor III, and In(Lu)-related p80, is currently thought to be involved in several steps of normal immune cell function, including lymphocyte adhesion to high endothelial venules and to the extracellular matrix and T cell activation. We now demonstrate that triggering of CD44 on T lymphocytes by anti-CD44 mAb promotes cell adhesion. The induced homotypic adhesion is mediated by lymphocyte function-associated antigen-1 (LFA-1), because it was inhibited by anti-LFA-1 antibodies and not by anti-LFA-3 antibodies. This notion is supported by the temperature and Mg2+ dependence which is characteristic of LFA-1-mediated adhesion. Moreover, the sensitivity of CD44-induced adhesion to AMG and H7, which both prevent the activation of protein kinase C, and to cytochalasin B, which inhibits microfilament formation, suggests that the activation of the LFA-1 pathway via CD44 involves protein kinase C activation and requires an intact cytoskeleton.

Antibodies, Monoclonal↗
PubMed1989

Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes.

The lymphocyte function-associated molecule LFA-1 (CD11a/CD18) plays a key part in lymphocyte adhesion. Lymphocytes do not adhere spontaneously; activation of protein kinase C (PKC) by phorbol esters, however, gives rise to strong LFA-1-dependent adhesion, indicating that activation of LFA-1 is required to induce cell adhesion. We have now investigated whether the functionally important CD2 and CD3 surface structures on T lymphocytes are involved in the activation of LFA-1. The stimulation of these molecules, which causes activation of PKC, strongly promoted LFA-1-dependent adhesion. Furthermore, we demonstrate by using cells from an LFA-1-deficient patient that this enhanced lymphocyte adhesion is caused by activation of the LFA-1 molecule and not by activation of its ligands. LFA-1 was persistently activated by triggering through CD2 but only transiently by triggering through CD3. We postulate that CD2 and CD3 can differentially regulate the affinity of LFA-1 for its ligands by modulating its molecular conformation through PKC-dependent mechanisms.

Antigens, CD↗
PubMed1987

Humoral and cellular immune responsiveness to human S-antigen in uveitis.

Purified human retinal S-antigen (S-ag) was used to investigate the occurrence of humoral and cellular autoimmune reactions against S-ag in uveitis patients. With a sensitive ELISA method anti-S-ag antibodies could be detected in the sera of 28% of the uveitis patients. No difference was found between patients with posterior or panuveitis (31 out of 117 positive) and patients with anterior or intermediate uveitis (16 out of 52 positive). Similar frequencies and levels of anti-S-ag autoantibodies were also found among healthy controls (6/20) and patients who had undergone cataract surgery (6/17). Immunoblotting with purified S-ag and with whole human retinal extract confirmed the presence of anti-S-ag antibodies in uveitis and control sera. Moreover, antibodies against various other retinal proteins could also be demonstrated in patients and controls, without being particularly enhanced in uveitis. The cellular immune responsiveness was tested by measuring the production of migration inhibitory factor (MIF) during overnight culture of peripheral mononuclear cells with the antigen. None of 18 healthy controls responded, whereas 17 positive reactions were observed in the group of 44 uveitis patients. The highest frequencies were found in patients with posterior (5/12) or pan- (7/12) uveitis, while of the responders with anterior (2/8) or intermediate (3/12) uveitis, three had disorders affecting the retina. Thus, cellular autoimmune responsiveness to S-ag is apparently associated with posterior and pan-uveitis, and might also occur in non-uveitic retinal disorders, whereas the occurrence of anti-S-ag antibodies is probably not at all pathognomic for uveitis.

Adolescent↗
PubMedDate not supplied

Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil beta2 integrin expression, adhesion, and degranulation.

BACKGROUND: To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. METHODS: Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. RESULTS: Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). CONCLUSIONS: LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.

Adult↗