Demonstration of a direct inhibitory effect of cyclosporine on normal human T-cells with two novel models of T-cell activation as probes

P. Sehajpal, A. Subramaniam, V. K. Murthi, V. K. Sharma, Manikkam Suthanthiran

Research output: Contribution to journalArticle

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Abstract

Two novel models of activation of human peripheral blood quiescent T-cells (T-cells) were utilized herein as probes to analyze the mechanisms and to locate the site of action of cyclosporine (CsA) in the T-cell activation pathway. Highly purified T-cells were activated, independently of accessory cells, with either crosslinked anti-CD2 + anti-CD3 monoclonal antibodies (mAbs) or with sn-1,2-dioctanoylglycerol (DAG) and ionomycin. CsA inhibited the expression of 55-kDa interleukin-2 receptors (IL-2R) and T-cell proliferation in these accessory cell-independent models of T-cell activation. Recombinant IL-2, over a wide range of concentrations that included different binding affinities of cellular receptors for IL-2, did not completely reverse CsA-associated inhibition of IL-2R expression and/or proliferation. In additional experiments, designed to examine early activation related events, CsA did not interfere with the increase in intracellular free calcium concentration initiated with anti-CD2, anti-CD3, anti-CD2 + anti-CD3 mAbs or with ionomycin. DAG-induced and PKC-activation-dependent down-regulation of cell surface expression of CD3 antigens was similarly unaffected by CsA. Our findings unambiguously indicate that CsA has a direct inhibitory effect on T-cells. Moreover, CsA's cellular site of action is distal to calcium mobilization and PKC activation but proximal to IL-2R expression and IL-2-dependent DNA synthesis in normal human T-cells.

Original languageEnglish
Pages (from-to)195-204
Number of pages10
JournalCellular Immunology
Volume120
Issue number1
DOIs
Publication statusPublished - 15 Apr 1989
Externally publishedYes

Fingerprint

Cyclosporine
T-Lymphocytes
Interleukin-2 Receptors
Ionomycin
Interleukin-2
Monoclonal Antibodies
CD3 Antigens
Calcium
Down-Regulation
Cell Proliferation
DNA

ASJC Scopus subject areas

  • Immunology

Cite this

Demonstration of a direct inhibitory effect of cyclosporine on normal human T-cells with two novel models of T-cell activation as probes. / Sehajpal, P.; Subramaniam, A.; Murthi, V. K.; Sharma, V. K.; Suthanthiran, Manikkam.

In: Cellular Immunology, Vol. 120, No. 1, 15.04.1989, p. 195-204.

Research output: Contribution to journalArticle

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