Histiocytic necrotizing lymphadentis (HNL) is a benign, self-limiting disorder that is characterized histologically by proliferation of large blastoid T cells and histiocytes and by cell death showing karyorrhectic nuclear debris. Recent articles have shown that the main form of cell death in HNL is apoptosis though it remains unclear whether the apoptotic cells are CD4-positives T cells (helper/inducer T cells) or CD8-positive T cells (cytotoxic T cells). In addition, the mechanism of apoptosis in HNL has not been clarified. In the present study, to elucidate the cell type of apoptotic cells and the possible activation mechanism of apoptosis, 40 cases of HNL were analyzed using the TUNEL method and immunohistochemical and ultrastructural techniques. The large lymphocytes in the involved areas were mainly CD8-positive cells, while the majority of apoptotic cells detected by the TUNEL method were CD4-positive cells, and a small number of apoptotic cells were CD8-positive cells. B and NK cells were rarely seen in the involved areas. Double immunostaining revealed that many CD8-positive large lymphocytes expressed perforin and/or granzyme B and that the majority of CD4-positive small lymphocytes were positive for caspase 3 (CPP32), the farthest downstream apoptosis inducer, which is critical to induction, but not for bcl-2. The CD4/CD8 ratio in CPP32-positive cells inversely correlated with the duration from the onset to the pathologic diagnosis in 7 cases of short duration up to 20 days (r=-0.76, p<0.05).
These findings suggest that in the early stage of HNL, the apoptosis of CD4-positive helper T cells is induced via the perforin and/or granzyme B pathway of activated CD8-positive cytotoxic T cells and that expression of caspase 3 (CPP32) and reduction of bcl-2 protein may be associated with the event of apoptotic cell death in HNL.

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