Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients.
Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic paraparesis is a demyelinating inflammatory neurologic disease associated with HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig complex to directly visualize HTLV-1 Tax11-19-specific T cells from peripheral blood and cerebrospinal fluid without in vitro stimulation. Five of six HTLV-1-associated myelopathy/tropic spastic paraparesis patients carried a significant number (up to 13.87%) of CD8(+) lymphocytes specific for the HTLV-1 Tax11-19 peptide in their peripheral blood, which were not found in healthy controls. Simultaneous comparison of peripheral blood and cerebrospinal fluid from one patient revealed 2.5-fold more Tax11-19-specific T cells in the cerebrospinal fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11-19-specific T cells were seen consistently over a 9-yr time course in one patient as far as 19 yrs after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11-19-specific CD8(+) T lymphocytes in HAM/TSP patients showed different expression patterns of activation markers, intracellular TNF-alpha and gamma-interferon depending on the severity of the disease. Thus, visualization of antigen-specific T cells demonstrates that HTLV-1 Tax11-19-specific CD8(+) T cells are activated, persist during the chronic phase of the disease, and accumulate in cerebrospinal fluid, showing their pivotal role in the pathogenesis of this neurologic disease.
Greten
T F
TF
Department of Oncology and Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 364, Baltimore, MD 21205, USA. tgreten@welchlink.jhu.edu
Slansky
J E
JE
Kubota
R
R
Soldan
S S
SS
Jaffee
E M
EM
Leist
T P
TP
Pardoll
D M
DM
Jacobson
S
S
Schneck
J P
JP
D005434:Flow Cytometry; D016356:Gene Products, tax / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology / Q000473:pathology; D015368:Human T-lymphotropic virus 1; D006801:Humans; D019044:Image Cytometry; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D015493:Paraparesis, Tropical Spastic / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D016356:Gene Products, tax; D015789:HLA-A2 Antigen