CXCR3/CXCL10 Axis-Mediated T Cell Infiltration in the Lungs of Patients With HTLV-1-Associated Diseases: Implications for Subclinical Pulmonary Involvement.

HTLV-1 is a retrovirus associated with adult T cell leukemia/lymphoma (ATL) and inflammatory diseases, including HTLV-1-associated myelopathy (HAM) and HTLV-1-associated bronchopneumonopathy (HAB). Although pulmonary complications are common in HTLV-1-associated diseases, the underlying mechanisms remain unclear. We compared HTLV-1 proviral load (PVL) and chemokine receptor expression in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers (ACs) and patients with HAB, HAM, or ATL. T cell subsets were analyzed by flow cytometry, and the expression of CXCR3 and CXCL10 in lung tissue was assessed by immunohistochemistry. HTLV-1 proviral DNA was detectable in BAL cells not only from HAB and ATL cases with pulmonary involvement, but also from some ACs and HAM cases without clinical respiratory symptoms, suggesting subclinical pulmonary infiltration. BAL samples from HAB and ATL showed increased CD8 + T cell frequency. Both CD4+ and CD8 + T cells in BAL expressed higher CXCR3 than their PBMC counterparts, whereas CCR4 and CXCR5 were not elevated. CADM1 + CD4 + T cells in BAL also exhibited higher CXCR3 than in PBMCs, and CXCR3+ frequencies were similar between CADM1+ and CADM1- CD4 + T cells within BAL, indicating that enhanced CXCR3 expression was largely independent of infection status. Histology revealed CD3+ mononuclear cell infiltration in alveolar septa and peribronchiolar regions in HAB and HAM, consistent with T cell-mediated alveolitis and bronchiolitis, and CXCL10 expression was elevated in infiltrated lesions. Collectively, these findings implicate the CXCR3/CXCL10 axis as a common pathway for pulmonary T cell recruitment in HTLV-1-associated diseases.