Lymphocyte transformation test: History and current approaches.

Area of Science:

• Immunology
• Pharmacology
• Clinical Medicine

Background:

• Drug-induced hypersensitivity reactions (DIHRs) present diverse clinical outcomes, ranging from mild rashes to life-threatening events.
• DIHRs are categorized as allergic (drug allergy) or non-allergic hypersensitivity.
• Drug allergies can be mediated by antibodies (e.g., IgE) or T cells.

Purpose of the Study:

• To review the historical development of the lymphocyte transformation test (LTT) for diagnosing drug allergies.
• To summarize modifications and variations of the LTT platform and its readout parameters over time.
• To highlight the LTT's role in the in vitro detection of drug-specific T cell responses.

Main Methods:

• The review synthesizes published literature on the lymphocyte transformation test (LTT).
• It describes the classical LTT methodology involving patient peripheral mononuclear cells (PMBCs) and suspected drugs.
• Focus is placed on T cell proliferation as a key readout parameter, historically measured by radiolabeled thymidine incorporation.

Main Results:

• The classical LTT relies on detecting drug-specific memory T cell activation and proliferation in vitro.
• Various modifications to LTT protocols, readout methods, and platform variations have been developed.
• These advancements aim to improve the accuracy and scope of in vitro drug allergy diagnostics.

Conclusions:

• The lymphocyte transformation test (LTT) is a valuable tool for the in vitro diagnosis of drug allergies.
• Understanding LTT's evolution and modifications is crucial for its effective application.
• Continued research and refinement of LTT are essential for advancing drug hypersensitivity diagnostics.