Direct evidence for a chronic CD8+-T-cell-mediated immune reaction to tax within the muscle of a human T-cell leukemia/lymphoma virus type 1-infected patient with sporadic inclusion body myositis.
Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection can lead to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), concomitantly with or without other inflammatory disorders such as myositis. These pathologies are considered immune-mediated diseases, and it is assumed that migration within tissues of both HTLV-1-infected CD4(+) T cells and anti-HTLV-1 cytotoxic T cells represents a pivotal event. However, although HTLV-1-infected T cells were found in inflamed lesions, the antigenic specificity of coinfiltrated CD8(+) T cells remains to be determined. In this study, we performed both ex vivo and in situ analyses using muscle biopsies obtained from an HTLV-1-infected patient with HAM/TSP and sporadic inclusion body myositis. We found that both HTLV-1-infected CD4(+) T cells and CD8(+) T cells directed to the dominant Tax antigen can be amplified from muscle cell cultures. Moreover, we were able to detect in two successive muscle biopsies both tax mRNA-positive mononuclear cells and T cells recognized by the Tax11-19/HLA-A*02 tetramer and positive for perforin. These findings provide the first direct demonstration that anti-Tax cytotoxic T cells are chronically recruited within inflamed tissues of an HTLV-1 infected patient, which validates the cytotoxic immune reaction model for the pathogenesis of HTLV-1-associated inflammatory disease.
Ozden
Simona
S
Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Paris, France.
Cochet
Madeleine
M
Mikol
Jacqueline
J
Teixeira
Antonio
A
Gessain
Antoine
A
Pique
Claudine
C
D000328:Adult; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D005260:Female; D016356:Gene Products, tax / Q000276:immunology*; D015234:HLA-A Antigens / Q000378:metabolism; D015490:HTLV-I Infections / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007181:Inclusion Bodies, Viral; D008562:Membrane Glycoproteins / Q000032:analysis; D008969:Molecular Sequence Data; D009132:Muscles / Q000473:pathology / Q000821:virology; D009220:Myositis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000821:virology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D016356:Gene Products, tax; D015234:HLA-A Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D054353:Perforin