Effect of immunosuppressants on OKT3 associated T cell activation

Clinical implications

Manikkam Suthanthiran, M. E. Wiebe, K. H. Stenzel

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The monoclonal antibody directed at the T cell differentiation antigen T3 (CD3, T.gp 20-25) appears to be superior to conventional high-dose steroids in the treatment of rejection in cadaveric renal graft recipients. Re-rejection episodes and other adverse reactions, probably secondary to T cell activating potential of anti-T3, continue to be clinical problems with anti-T3 therapy. We therefore examined the relative efficacy of cyclosporin A (CSA), methylprednisolone (MP), or 6-mercaptopurine (6-MP), at concentrations that are readily accomplished in clinical practice, on the activation of T cells by anti-T3. CSA or MP mediated marked and 6-MP mediated modest inhibition of anti-T3 induced proliferation of alloimmune memory T cells. CSA- or MP-inhibited anti-T3 elicited specific secondary cytolytic activity and natural killer (NK) cell activity, and 6-MP failed to prevent the augmentation of NK cell activity mediated by anti-T3. The immunosuppressants also exhibited differential effects on anti-T3-associated lymphokine production by peripheral blood mononuclear cells. Interleukin 2 production was completely inhibited by CSA, modestly inhibited by MP and not inhibited by 6-MP. Interferon gamma production was completely inhibited by CSA or MP and not inhibited by 6-MP. Our findings, in addition to providing a plausible immunological basis for some of the complications of anti-T3 therapy, provide experimental support for therapeutic strategies that include the use of CSA and/or MP along with anti-T3.

Original languageEnglish
Pages (from-to)362-367
Number of pages6
JournalKidney International
Volume32
Issue number3
DOIs
Publication statusPublished - 1 Jan 1987
Externally publishedYes

Fingerprint

Muromonab-CD3
Methylprednisolone
6-Mercaptopurine
Immunosuppressive Agents
Cyclosporine
T-Lymphocytes
Natural Killer Cells
T Lymphocyte Differentiation Antigens
Investigational Therapies
Lymphokines
Interferon-gamma
Interleukin-2
Blood Cells
Therapeutics
Steroids
Monoclonal Antibodies
Transplants
Kidney

ASJC Scopus subject areas

  • Nephrology

Cite this

Effect of immunosuppressants on OKT3 associated T cell activation : Clinical implications. / Suthanthiran, Manikkam; Wiebe, M. E.; Stenzel, K. H.

In: Kidney International, Vol. 32, No. 3, 01.01.1987, p. 362-367.

Research output: Contribution to journalArticle

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