Increased HTLV type 1 tax specific CD8+ cells in HTLV type 1-asociated myelopathy/tropical spastic paraparesis: correlation with HTLV type 1 proviral load.
Less than 1% of individuals infected with the human T lymphotropic virus type 1 (HTLV-1) develop an inflammatory neurological disorder, termed HTLV-1-associated myelopathy/tropical spastic (HAM/TSP), while the vast majority of those infected remain asymptomatic HTLV-1 carriers (ACs). The fundamental viroimmunological differences between these groups are not well understood. To address this issue, we have investigated HTLV-1-specific T cell responses and measured the proviral load in these groups. Frequencies of HTLV-1-specific CD8(+) cells were demonstrated to be significantly higher in HAM/TSP patients than in ACs by using intracellular cytokine staining and soluble divalent HLA-A2/Ig fusion protein loaded with HTLV-1 Tax 11-19 peptide. It is consistent with the observed increase in HTLV-1-specific cytotoxic T lymphocytes in HAM/TSP patients. These CD8(+) cells produced interferon (IFN)-gamma in recognition of HTLV-1 antigens bound to HLAs on the infected CD4(+) cells. Using phenotypic markers indicative for T cell differentiation, memory and/or effector HTLV-1 Tax-specific CD8(+) cells were found to be increased in HLA-A2 HAM/TSP patients. HTLV-1 proviral load was elevated in HAM/TSP patients when compared to ACs. In addition, the proviral load in HAM/TSP patients correlated with the frequency of HTLV-1-specific IFN-gamma(+)CD8(+) cells or Tax-HLA-A2/Ig(+)CD8(+) cells, especially with the effector cells. In contrast, the proviral load inversely correlated with memory cells. These results suggest that HTLV-1 antigens may continuously stimulate HTLV-1-specific CD8(+) cells and differentiate them from memory cells into effector cells in vivo. These differentiated HTLV-1-specific CD8(+) cells may play a role in the pathogenesis of HAM/TSP.
Kubota
R
R
Viral Immunology Section, NIB, NINDS, NIH, Bethesda, Maryland 20892, USA.
Nagai
M
M
Kawanishi
T
T
Osame
M
M
Jacobson
S
S
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002353:Carrier State / Q000276:immunology / Q000821:virology; D016356:Gene Products, tax / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000821:virology; D011533:Proviruses / Q000502:physiology; D019562:Viral Load
D016356:Gene Products, tax; D007371:Interferon-gamma