Lymphocyte surface poisons: disulfides and thiolsulfonates.

Area of Science:

• Immunology
• Pharmacology

Background:

• Graft-versus-host reactions (GvHR) are a significant complication in allogeneic transplantation.
• Identifying agents that selectively target lymphocytes involved in GvHR without causing systemic toxicity is crucial.

Purpose of the Study:

• To evaluate novel disulfide and thiolsulfonate compounds as potential blocking agents for lymphocytes in GvHR.
• To assess the specificity and efficacy of these agents in inhibiting GvHR while minimizing intracellular effects.

Main Methods:

• Lymphocytes were incubated with candidate agents and their ability to inhibit local GvHR in F1 hybrid offspring was measured.
• Intracellular effects were assessed by measuring inhibition of [6-3H]thymidine incorporation into lymphocytes.
• Structural specificity was evaluated using a panel of related chemical compounds.

Main Results:

• Eight disulfides and one thiolsulfonate demonstrated significant GvHR blocking activity at concentrations causing minimal [6-3H]thymidine incorporation inhibition (approx. 50%).
• Cellular survival remained high (≥90%) in GvHR tests, even with significant thymidine incorporation inhibition.
• Structural analysis revealed specificity for active compounds, with related compounds showing little to no activity.

Conclusions:

• Disulfides and thiolsulfonates can effectively inhibit GvHR by acting as cell-surface poisons.
• These agents represent promising leads for developing novel immunosuppressive or anti-leukemic therapies.
• The mechanism likely involves modification of cell-surface thiol groups.