The impact of acemannan on the generation and function of cytotoxic T-lymphocytes.
Acemannan, an antiviral agent with immune enhancement capabilities, was studied for its impact on cytotoxic T-lymphocyte (Tc) function generated in response to alloantigen. To investigate whether acemannan directly stimulated the generation of Tc from primary mixed lymphocyte cultures (MLC), the drug was added at the initiation of the MLC. There was a dose-related, statistical increase in killer T-cell generation produced by acemannan in the clinically relevant dose range. The lowest test dose of the drug (2.6 x 10(-9) M) increased chromium release nearly two-fold; the 2.6 x 10(-8) M dose gave a maximal 3.5 fold increase in cytotoxic T-cells. To study whether acemannan enhanced the capacity of Tc once generated to alloantigen to destroy targets bearing the sensitizing antigens, MLR were established in the absence of any drug. Acemannan at the two highest doses increased the functional capacity of Tc to destroy target cells to which they had been sensitized in the MLR. To control for the possibility that acemannan was directly cytotoxic to target cells, targets were incubated alone with drug and without sensitized killer T-cells. No dose of acemannan was found to be cytotoxic to these cells. In conclusion, acemannan did enhance the generation of cytotoxic T-cells when added at the initiation of the MLR. When acemannan was added at the completion of allostimulation, an increase of almost 50% killing by Tc was also observed. These effects can not be explained by direct drug related toxicity and suggest a functional correlate to the previously described immune enhancing properties of the agent. As this drug is being tested for the treatment of HIV infections, these data provide at least one immunologic mechanism by which acemannan may be clinically salutory.
Womble
D
D
Department of Internal Medicine, Vanderbilt University, Nashville, Tennessee 37232-2372.
Helderman
J H
JH
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008351:Mannans / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000502:physiology
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D008351:Mannans; C058414:acemannan