PubMed Health⌕ Search

Biomedical subjects

K M Jackson

Publications and source records attributed to K M Jackson.

7 recordsLinked to original sources
PubMed1989

Two distinct mechanisms of interleukin-2 gene expression in human T lymphocytes.

Interleukin-2 (IL-2) gene regulation was investigated in primary cultures of highly purified human peripheral blood CD28+ T cells. Two discrete mechanisms for induction of T-cell proliferation could be distinguished by examining cell cycle progression and the expression of the IL-2 gene. Stimulation of cells by CD3 MoAb induced only transiently expressed, small amounts of IL-2 mRNA that was completely suppressed by cyclosporine. Costimulation of T cells with CD3 MoAb and either CD28 MoAb or PMA, but not calcium ionophore, induced a 50-100-fold increased in IL-2 gene expression and secretion. High levels of IL-2 gene expression could also be achieved by stimulation with calcium ionophore and PMA or CD28 MoAb and PMA, but not by CD28 MoAb plus calcium ionophore. IL-2 gene expression and T-cell proliferation induced by CD3 MoAb plus PMA or calcium ionophore plus PMA were completely suppressible by cyclosporine. In contrast, IL-2 gene expression and T-cell proliferation induced by CD28 MoAb plus PMA were unaffected by cyclosporine. The CD28 signal was dependent on new protein synthesis. Nuclear run-on transcription assays showed that anti-CD28 did not affect lymphokine transcription. A major effect of CD28 stimulation on mRNA stability was shown by studies using actinomycin D; CD28 stimulation substantially increased the half-life of IL-2 and TNF-alpha mRNA. The effects of anti-CD28 stimulation were specific for growth factors, and thus differ from previously described effects of cycloheximide on mRNA stability. These studies suggest the existence of two biochemical pathways for the induction of IL-2 production, one that occurs at the transcriptional level and is mediated by intracellular calcium release and protein kinase C and is cyclosporine-sensitive, and one that acts post-transcriptionally, is mediated by CD28 stimulation, and is cyclosporine-resistant.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Gangliosides suppress the proliferation of autoreactive cells in experimental allergic encephalomyelitis: ganglioside effects on IL-2 activity.

Gangliosides have been shown to suppress human and murine lymphocyte proliferative responses in vitro. We tested the suppressive effects of gangliosides on the proliferation of autoreactive lymphoid cells obtained from Lewis rats with experimental allergic encephalomyelitis (EAE). Exogenous rat brain gangliosides inhibited both antigen- and mitogen-induced proliferation by as much as 79 and 93%, respectively. Gangliosides similarly inhibited the antigen-induced proliferation of a myelin basic protein (MBP)-reactive T-cell line which is able to passively induce EAE. Suppression was greatest when gangliosides were added at the initiation of culture, and was not abrogated by supraoptimal antigen concentration. Interleukin 2 (IL-2) activity in culture supernatants was not diminished by the addition of gangliosides. Gangliosides did not inhibit the IL-2-induced proliferation of a murine IL-2-dependent cell line, CTLL-20, unless the IL-2 was first preincubated with gangliosides before the addition of CTLL-20. Preincubation of CTLL-20 with gangliosides resulted in no inhibition of the subsequent responses to IL-2. Exogenous gangliosides did not decrease the binding of a monoclonal antibody directed against the rat cell surface IL-2 receptor. Addition of exogenous IL-2 to ganglioside-suppressed cultures had no effect or only partially restored the proliferative responses. Therefore, gangliosides were shown to inhibit the proliferation of autoreactive lymphoid cells without affecting IL-2 production or IL-2 receptor expression.

Animals↗