Biomedical subjects

Y Martin

Publications and source records attributed to Y Martin.

At least 37 records · Page 2Linked to original sources

PubMed1992

Prolonged IL-2 receptor alpha/CD25 expression after T cell activation via the adhesion molecules CD2 and CD28. Demonstration of combined transcriptional and post-transcriptional regulation.

The T cell adhesion molecule CD28 provides a costimulatory signal in combination with CD2 and CD3 mAb. CD28 regulates the expression of cytokines by T cells, not only IL-2, but also IL-1 alpha and CSF-1, usually synthesized by accessory cells. We have investigated the mechanisms through which CD28 modulates the expression of the IL-2R alpha chain. Whereas activation through CD2 or CD28 alone induced no or only low IL-2R alpha chain expression, activation through CD2 plus CD28 led to both a high and prolonged (greater than 14 days) cell surface and mRNA expression. In contrast, immobilized CD3 mAb-dependent activation induced a transient expression of the IL-2R alpha chain, which was neither further increased nor prolonged by CD28 costimulation. Upon CD2 plus CD28 stimulation, the half-lives of the two IL-2R alpha transcripts increased progressively between days 1 and 4, in contrast to each pathway alone. Whereas each activation pathway alone induced either no (CD2) or low (CD28) levels of IL-2R alpha gene transcription, the CD2 plus CD28 stimulation was associated with its increased transcription, which persisted at similar rates between 5 and 96 h post stimulation. The in vitro costimulation via the CD2 and CD28 molecules thus regulates the expression of the IL-2R alpha gene both at the transcriptional and post transcriptional levels. Our results therefore demonstrate a new immunoregulatory function of the CD28 molecule on IL-2R alpha expression, which, through its increased transcription rate and stabilization, could, together with high levels of cytokines secretion, be responsible for the prolonged T cell proliferation.

Antigens, CD↗

PubMed1992

Contributions of the CD2 and CD28 T lymphocyte activation pathways to the regulation of the expression of the colony-stimulating factor (CSF-1) gene.

The T cell adhesion molecule CD28 provides a costimulatory signal, in combination with either CD2 or CD3 mAb. CD28 appears to regulate the expression, by T cells, of cytokines normally produced by accessory cells, namely IL-1 alpha, TNF-alpha, and CSF-1. The CSF-1 gene is expressed as a 4.0-kb transcript by human T cells activated with mAb directed against CD2 and CD28, alone or in combination. A kinetic analysis of its expression showed low steady-state levels of the transcript after CD2 stimulation, and a transient rise after CD28 stimulation. In contrast, a mean fivefold increase in the levels of the transcript was detected in CD2 plus CD28-stimulated cells. The potential mechanisms regulating this increase were investigated. The half-life of the CSF-1 transcript was identical in cells activated with either CD28 or CD2 plus CD28. Transcription of the CSF-1 gene appeared to undergo attenuation in resting cells as well as in cells activated via a single pathway; this attenuation was relieved in part by the combined CD2 plus CD28 stimulation. Thus in vitro costimulation via the CD2 and CD28 molecules regulates the expression of the CSF-1 gene mainly at the transcriptional level.

Antigens, CD↗

PubMed1991

IL-1 alpha is produced by T lymphocytes activated via the CD2 plus CD28 pathways.

In addition to activation via the TCR complex, resting purified T cells can be activated to proliferate by mAb directed against the two surface molecules, CD2 and CD28. We demonstrate here that only the CD2 plus CD28 combined activation induces the expression and secretion of IL-1 alpha, a cytokine classically considered as a monokine. In contrast, neither IL-1 beta nor IL-6 were produced. A second monokine, TNF-alpha was transiently expressed by T cells activated with either CD2 or CD28 mAb, but was expressed to higher levels and with a prolonged kinetics in cells activated by the CD2 plus CD28 combination. The prolonged expression of the IL-1 alpha gene could account, at least in part, for the monocyte-independent and long lasting T cell proliferation induced by the CD2 plus CD28 co-stimulation. Secretion of monokines, such as IL-1 alpha, by activated T cells, could play a regulatory role in immune responses, as well as contribute to autoimmune processes.

Antigens, CD↗

PubMed1989

Inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships.

Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids.

Acetylation↗

PubMed1974