Antithymocyte globulin reacts with many normal human cell types.

Area of Science:

• Immunology
• Hematology

Background:

• Antithymocyte globulin (ATG) is a common therapy for aplastic anemia.
• Its mechanism of action is often presumed to involve inhibition of lymphocytes.
• The preparation method of ATG does not suggest specificity for T lymphocytes.

Purpose of the Study:

• To investigate the binding specificity of Antithymocyte globulin (ATG).
• To determine the cellular targets of ATG beyond lymphocytes.
• To clarify the mechanism of action for ATG in aplastic anemia treatment.

Main Methods:

• Flow microfluorometry and fluorescence immunohistochemistry were used to assess ATG binding.
• Absorption studies with granulocytes and lymphocytes were performed.
• Monoclonal antibody binding inhibition assays were conducted.
• In vitro cytotoxicity assays were performed on various cell types.

Main Results:

• ATG binds to lymphocytes, granulocytes, platelets, and bone marrow cells.
• Absorption studies indicate distinct antigens recognized on different cell types.
• ATG treatment blocks binding of antibodies to lymphocyte differentiation and histocompatibility antigens.
• ATG exhibits in vitro cytotoxicity against T and non-T lymphocytes and platelets.
• ATG also binds to visceral tissues.

Conclusions:

• Antithymocyte globulin (ATG) is not specific for T lymphocytes.
• ATG interacts with a wide range of hematopoietic cells and tissues.
• The therapeutic effects of ATG in aplastic anemia may involve multiple cell types.
• It is premature to attribute the mechanism of action of ATG solely to a specific lymphocyte population.