A reappraisal of the effects of monoclonal antibodies directed at t cell differentiation antigens

Manikkam Suthanthiran, Monica Evelyn, Albert L. Rubin, Kurt H. Stenzel

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Abstract

We examined the effects of monoclonal antibodies (Abs) directed at T3 antigen (expressed on most postthymic T cells), T4antigen (helper/inducer subset) and T8 antigen (suppressor/cytotoxic subset). Anti-T3 induced interleukin-2 production and proliferation of peripheral blood mononuclear cells (PBM). Anti-T4 or T8 did not exhibit such properties. Addition of methylpred-nisolone (MP) or cyclosporine (CsA) to PBM activated with anti-T3 resulted in 79% and 88% suppression of proliferation, respectively. Neither anti-T4 nor anti-T8 mediated significant inhibition of anti-T3-induced proliferation. Primary mixed lymphocyte cultures (MLC) were variably affected by Abs. Anti-T3 augmented proliferation found in primary MLCs aT48 hr and had an inconsistent effect on the proliferative response found at 120–136 hr of culture. Primary cytotoxic T lymphocyte (CTL) generation was consistently suppressed by anti-T3, while natural killer (NK)-cell-like activity was augmented at 72 hr and suppressed after 136 hr of culture. Anti-T4 mediated a dose-dependent suppression of proliferation and CTL generation in the primary MLC and had minimal effect on the induction of NK-cell-like activity. At high concentrations (5000–1000 ng/ml), anti-T8 mediated modest inhibition of proliferation and of the induction of cytolytic activity.Alloimmune memory cells, generated in long-term primary MLCs, were activated by anti-T3to exhibit specific secondary cytolytic activity and NK-cell-like activity in the absence of the original priming stimulus. Neither anti-T nor anti-T, under identical experimental conditions, activated memory cells. When interrelated, our experimental findings indicated that: (1) the ultimate immunity elicited by anti-T antigen interaction is critically dependent upon the immune potential of the cell assessed; (2) MP or CsA can inhibit PBM activation by anti-T; and (3) anti-T4might have a role as an immunosuppressant in renal graft recipients.

Original languageEnglish
Pages (from-to)720-726
Number of pages7
JournalTransplantation
Volume38
Issue number6
DOIs
Publication statusPublished - 1 Jan 1984
Externally publishedYes

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ASJC Scopus subject areas

  • Transplantation

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