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Integration of the human lymphocyte into immunotoxicological investigations

S C Wood1, J G Karras, M P Holsapple

  • 1Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.

Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology
|April 1, 1992
PubMed

Insights

Human lymphocytes (HTL) show similar responses to xenobiotics as murine splenocytes (SPLC), validating HTL as an in vitro immunotoxicology model. This study compared immunosuppressive effects of acetoxydimethylnitrosamine (ACDMN), acrolein (ACR), and TCDD on both cell types.

Area of Science:

  • Immunotoxicology
  • In vitro toxicology
  • Cellular immunology

Background:

  • Xenobiotics like acetoxydimethylnitrosamine (ACDMN), acrolein (ACR), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are known immunosuppressors of murine splenocytes.
  • Evaluating the immunotoxic potential of xenobiotics on human cells is crucial for human health risk assessment.
  • Establishing reliable in vitro models using human cells is essential for immunotoxicological investigations.

Purpose of the Study:

  • To determine if human lymphocytes can be modulated by direct exposure to ACDMN, ACR, and TCDD.
  • To compare the immunomodulatory effects of these xenobiotics on human tonsillar lymphocytes (HTL) and murine splenocytes (SPLC).
  • To assess the utility of HTL as an in vitro model system for immunotoxicological studies.

Main Methods:

  • Comparison of xenobiotic activity on cultured murine splenocytes (SPLC) and human tonsillar lymphocytes (HTL).
  • Assays included anti-sheep erythrocyte IgM response, pokeweed mitogen (PWM)-induced proliferation, and antibody-forming cell (AFC) responses.
  • Evaluated concentrations ranged from nanomolar to micromolar for ACDMN, ACR, and TCDD.

Main Results:

  • ACDMN inhibited responses in both SPLC and HTL at 0.1-10 microM.
  • ACR suppressed responses at 100 microM, with decreased cell viability.
  • TCDD inhibited the murine SPLC anti-SRBC IgM response but not PWM-induced proliferation or antibody production in either cell type; it reduced background proliferation in both SPLC and HTL.

Conclusions:

  • Human tonsillar lymphocytes (HTL) exhibit a comparable profile of activity to murine splenocytes (SPLC) when exposed to certain xenobiotics.
  • HTL can serve as a viable in vitro model for evaluating the direct immunotoxic potential of xenobiotics.
  • This finding supports the use of human-derived cell systems in immunotoxicological risk assessment.

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