Abundant tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes.
The role of the cellular immune response in human T-cell leukemia virus type I (HTLV-I) infection is not fully understood. A persistently activated cytotoxic T lymphocyte (CTL) response to HTLV-I is found in the majority of infected individuals. However, it remains unclear whether this CTL response is protective or causes tissue damage. In addition, several observations paradoxically suggest that HTLV-I is transcriptionally silent in most infected cells and, therefore, not detectable by virus-specific CTLs. With the use of a new flow cytometric procedure, we show here that a high proportion of naturally infected CD4+ peripheral blood mononuclear cells (PBMC) (between 10% and 80%) are capable of expressing Tax, the immunodominant target antigen recognized by virus-specific CTLs. Furthermore, we provide direct evidence that autologous CD8+ T cells rapidly kill CD4+ cells naturally infected with HTLV-I and expressing Tax in vitro by a perforin-dependent mechanism. Consistent with these observations, we observed a significant negative correlation between the frequency of Tax(11-19)-specific CD8+ T cells and the percentage of CD4+ T cells in peripheral blood of patients infected with HTLV-I. Those results are in accordance with the view that virus-specific CTLs participate in a highly efficient immune surveillance mechanism that persistently destroys Tax-expressing HTLV-I-infected CD4+ T cells in vivo. (Blood. 2000;95:1386-1392)
Hanon
E
E
Department of Immunology and Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, St Mary's Campus, London, United Kingdom.
Hall
S
S
Taylor
G P
GP
Saito
M
M
Davis
R
R
Tanaka
Y
Y
Usuku
K
K
Osame
M
M
Weber
J N
JN
Bangham
C R
CR
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology*; D016356:Gene Products, tax / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D018942:Macrolides; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*; D014158:Transcription, Genetic
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D016356:Gene Products, tax; D018942:Macrolides; D012333:RNA, Messenger; C036978:concanamycin A