| Abstract | An important challenge in the field of auto-immune diseases, bone marrow and organ transplantation is the control of T-lymphocyte activation. To gain more insight into the in vitro correlation of immunosuppression, we investigated the effects of cyclosporin A (CSA) and two other metabolic inhibitors on cytokine secretion and T-cell proliferation. Secretion of TNF-alpha and GM-CSF was much more resistant to metabolic inhibitors than proliferation or synthesis of IL-1 alpha or IL-2. Moreover, our data suggested that the regulation of IL-1 alpha production in T-cells was CSA and protein kinase C (PKC)-dependent, as opposed to monocytes regulation. The receptivity to the epithelial cell-derived cytokine IL-7, associated either with antigen-dependent or independent triggering, was almost similarly inhibited by cyclosporin A, forskolin or PKC inhibitor, in sharp contrast to IL-2 receptivity. In this latter case, CD28+ IL-2 stimulation was more sensitive to both forskolin and PKC inhibition than that of CD2 or CD3+ IL-2. With regard to CSA effects, limiting dilution analysis provided evidence for some heterogeneity at the clonal level. This strongly suggested that T-cell functional monitoring at the population level does not truly reflect the actual immunosuppression. Additional experiments are required to evaluate the sensitivity to metabolic inhibitors of T-lymphocyte activation via the natural ligands of CD2 and CD28. |
| Authors | R Costello, C Mawas, D Olive
(Affiliation: Unité INSERM U119, Marseille, France.)
|
| Journal | European cytokine network
(Eur Cytokine Netw)
1993 Mar-Apr
Vol. 4
Issue 2
Pg. 139-46
ISSN: 1148-5493 FRANCE |
| PMID | 8100456
(Publication Type: Comparative Study, In Vitro, Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antigens, CD
- Antigens, CD2
- Antigens, CD28
- Antigens, CD3
- Antigens, Differentiation, T-Lymphocyte
- Antimetabolites
- Cytokines
- Immunosuppressive Agents
- Indoles
- Interleukin-2
- Interleukin-7
- Maleimides
- Receptors, Immunologic
- bisindolylmaleimide I
- Cyclosporine
- Forskolin
- Protein Kinase C
|
| Topics |
- Antigens, CD
- Antigens, CD2
- Antigens, CD28
- Antigens, CD3
- Antigens, Differentiation, T-Lymphocyte
- Antimetabolites
(pharmacology)
- Cyclosporine
(pharmacology)
- Cytokines
(biosynthesis)
- Forskolin
(pharmacology)
- Humans
- Immunosuppressive Agents
(pharmacology)
- Indoles
(pharmacology)
- Interleukin-2
(pharmacology)
- Interleukin-7
(pharmacology)
- Lymphocyte Activation
(drug effects)
- Maleimides
(pharmacology)
- Protein Kinase C
(antagonists & inhibitors)
- Receptors, Immunologic
- T-Lymphocytes
(drug effects, immunology, metabolism)
|
