FoxP3, a Key Molecule in CD4+CD25+ Regulatory T Cells, Express in Adult T Cell Leukemia/Lymphoma Cells and Relates to Clinicopathological Features.

AIMES: Adult T cell leukemia/lymphoma (ATLL) is an aggressive neoplastic disease and opportunistic infections often occur in patients with ATLL. However, the underlying mechanisms of such infections remain unknown. Recently, regulatory T cells (Treg), characterized by coexpression of CD4 and CD25, are proposed as a new T cell group with definite function. Treg suppresses normal T cells proliferation in vitro and play an important role to suppress autoimmune disease in vivo. But the deregulated proliferation such immunosuppressive T cells may induce immunodeficient status. We analyzed the expression of forkhead/winged helix transcription factor (FoxP3), known to be important for the function and specific marker of Treg cells, on ATLL cells. METHODS and RESULTS: FoxP3 expression was detected in both peripheral blood and lymph nodes in part of ATLL cases by real-time PCR and immunostaining (Figure). Next, we immunostained lymph node sections from 112 cases and 36 cases showed positivity for FoXP3. Morphologically, 112 ATLL cases were divided into three variants, namely pleomorphic cell type (61 cases), large cell type (45 cases), and anaplastic large cell type (16 cases). FoxP3 was expressed (more than 30% of the lymphoma cells) in a proportion of pleomorphic cell type (24 cases, 39.4%) and large cell type (12 cases, 26.7%) but no cases of anaplastic type showed positivity. Especially, strong expression (more than 50% of the lymphoma cells) was observed in 15 cases and 12 cases were pleomorphic cell type (Table). A proportion of FoxP3 positive ATLL cases showed intermingled EBV-infected transformed lymphocytes, suggesting local immunodeficient condition (Very few FoxP3 negative cases showed EBV-infected lymphocytes)(Table). Clinically, more proportion of FoxP3 positive ATLL cases showed opportunistic infection, for example Pneumocystis Carinii infections, Herpes zoster virus infection, antibiotics-refractory abscesses (Table). CONCLUSION: A proliferation of FoxP3 positive lymphoma cells may contribute to the tumor invasion and opportunistic infection by inducing local and diffuse immunodeficient status respectively. Figure Figure