Human T‐lymphotropic virus type I (HTLV‐I)‐specific CD8+ cells accumulate in the lungs of patients infected with HTLV‐I with pulmonary involvement

Abstract

Pulmonary involvement has been identified in human T-lymphotropic virus type I (HTLV-I) carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, the relationship between HTLV-I infection and lung disease is poorly understood. The occurrence of HTLV-I-specific immune responses in the lungs of patients infected with HTLV-I with pulmonary involvement was investigated. The frequency of HTLV-I-specific CD8+ cells and the amount of HTLV-I proviral DNA were determined in bronchoalveolar lavage fluid cells and peripheral blood mononuclear cells (PBMCs) from five patients with HAM/TSP and one HTLV-I carrier who had pulmonary involvement. HTLV-I-specific CD8+ cells were detected by flow cytometry using human leukocyte antigen/antigen complex multimers. The analysis of bronchoalveolar lavage fluid revealed lymphocytosis in five of six patients. HTLV-I provirus was detected in the bronchoalveolar lavage fluid cells of all patients, and the proviral load in these cells was comparable to that in PBMCs. The frequency of HTLV-I-specific CD8+ cells in the bronchoalveolar lavage fluid cells was 5.1 times higher than that in PBMCs. Immunohistochemically, clusters formed by HTLV-I-specific CD8+ cells were detected in lung tissue by in situ tetramer staining. No samples were available from patients infected with HTLV-I without lung disorders. Whether accumulation of CD8+ cells is specific to patients with pulmonary involvement remains unclear. These results indicate that HTLV-I-specific CD8+ cells accumulate and HTLV-I-infected cells exist in the lungs of patients infected with HTLV-I with pulmonary involvement.

CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon

“…However, pulmonary involvement in HAM/TSP was first described in 1987 [ 2 ]. Since then, laboratory and radiological evidence have been demonstrated [ 2 , 4 , 10 , 11 , 12 ], although radiological and pulmonary function analyses involving patients with HAM/TSP, as done in this study, have not been previously performed. In addition, no study has been conducted among individuals from the Brazilian Amazon region.…”

“…On the other hand, the association between HTLV-1 infection and pulmonary changes is not clear [ 3 , 4 ]; only a few studies have been published, and none has been conducted yet in the Brazilian Amazon. Also, studies have not clearly defined whether patients with established systemic inflammation (e.g.…”

Higher Human T-Lymphotropic Virus Type 1 Subtype C Proviral Loads Are Associated With Bronchiectasis in Indigenous Australians: Results of a Case-Control Study

“…The high HTLV-1 PVL [ 30 ] of these cells was correlated with that of peripheral blood mononuclear cells [ 30 ]. The presence of HTLV-1-infected lymphocytes in BAL fluid is associated with increased HTLV-1 tax/rex mRNA expression in vivo [ 31 , 32 ], a proinflammatory milieu [ 32 ], and an HTLV-1-specific cytotoxic T cell-mediated inflammatory response among patients with HTLV-1-associated interstitial pneumonitis [ 33 ].…”

Inflammatory manifestations of HTLV-1 and their therapeutic options

“…HTLV-1 Tax protein is known to induce the expression of IL-2 [164,165]. A correlation between lymphocytosis, increased CD4 + CD25 + cells with tax mRNA [166], Foxp3 and HBZ mRNA expression [167] and CD8 + T cells in bronchoalveolar fluid was demonstrated in HTLV-1 carriers and HAM/TSP patients [168]. The presence of HTLV-1 infected cells in the alveoli seems to induce T-lymphocyte migration and clonal expansion leading to inflammation of pulmonary tissue through secretion of cytokines and chemokines [163].…”