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Related Experiment Videos

Recombinant human soluble CD4 does not inhibit immune function in cynomolgus monkeys.

P J Bugelski1, P A Thiem, A Truneh

  • 1Department of Experimental Pathology, SmithKline Beecham Pharmaceuticals, Philadelphia, Pennsylvania 19406.

Toxicologic Pathology
|January 1, 1991
PubMed
Summary

Recombinant soluble CD4 (sT4) therapy for HIV may impact lymphocyte function. Studies in cynomolgus monkeys found no evidence that sT4 suppresses immune responses, suggesting it is unlikely to be immunosuppressive in humans.

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Area of Science:

  • Immunology
  • Virology
  • Pharmacology

Background:

  • Recombinant soluble CD4 (sT4) inhibits HIV infectivity.
  • CD4's role in lymphocyte and MHC Class II antigen interaction raises concerns about potential immunosuppression with sT4 therapy.

Purpose of the Study:

  • To investigate the effects of sT4 on immune function in vivo and in vitro.
  • To assess potential immunosuppressive effects of sT4 on lymphocyte responses.

Main Methods:

  • Evaluated sT4 effects on mitogen-mediated blastogenesis and mixed lymphocyte reactions in cynomolgus monkeys.
  • Assessed delayed type hypersensitivity (DTH) reactions to dinitrochlorobenzene (DNCB) and analyzed lymphocyte subsets.

Main Results:

  • No evidence of sT4-mediated suppression on in vitro responses to mitogens (concanavalin A, phytohemagglutinin, pokeweed).

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  • No observed effects of sT4 on lymphocyte subsets or DTH responses in treated monkeys.
  • sT4 administration up to 100 mg/kg intravenously showed no immunosuppressive activity.

    • Conclusions:

    • Data suggest that sT4 is not immunosuppressive in cynomolgus monkeys.
    • Given conserved CD4 and MHC Class II antigen structures, sT4-like molecules are unlikely to cause immunosuppression in humans.