Inverse correlation of cyclosporine binding with sensitivity and resistance

Allan D. Hess, Paul Colombani

Research output: Contribution to journalArticle

Abstract

The primary effects of CsA on human lymphocyte responses in v it ro appear to be the inhibition o f IL-2 production and the inhibition o f cy to tox ic T cell activation. Induction o f suppressor T cell activity is resistant to the e f fe c ts of CsA. These data imply two distinct subsets o f lymphocytes: CsA-resistant and CsA-sensitive. The current studies used a bioact ive, dansylatedd e rivative o f CsA (dans-CsA), which is fluorescent, to assess binding o f CsA at the single-cell level by flow cytometry. The results demonstrate that tw o populations o f cells can be distinguished based on d if fe rential staining with dans CsA- a weakly staining subset and a population that binds intensely. Both subsets consist o f CD4 (helper) and CD8 (cytotoxic/suppressor) T lymphocytes. Functional analysis revealed that the weakly staining subset consists o f IL -2 -p rodu c in g T cells and precursor cy to to x ic T lymphocytes. On the other hand, the intensely staining subset includes T cells that suppress in an antigen-specific manner after activation with alloantigen. Further studies showed that the weak ly staining subset is markedly sensitive to the immunosuppressive e f fe c ts o f CsA in a PHA stimulation assay, whi le the intensely binding population is markedly resistant, requir ing 10- to 1 0 0 - fo ld more CsA to inhibit the PHA response. These studies suggest that sensitivity and resistance to CsA is inversely correlated with binding.

Original languageEnglish (US)
Pages (from-to)61S-67S
JournalTransplantation
Volume46
Issue number2
StatePublished - 1988

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Cyclosporine
Staining and Labeling
T-Lymphocytes
Interleukin-2
Lymphocytes
T-Lymphoid Precursor Cells
Population
Isoantigens
T-Lymphocyte Subsets
Cytotoxic T-Lymphocytes
Immunosuppressive Agents
Flow Cytometry
Antigens

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Inverse correlation of cyclosporine binding with sensitivity and resistance. / Hess, Allan D.; Colombani, Paul.

In: Transplantation, Vol. 46, No. 2, 1988, p. 61S-67S.

Research output: Contribution to journalArticle

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