title: HTLV-I specific IFN-gamma+ CD8+ lymphocytes correlate with the proviral load in peripheral blood of infected individuals.
abstract: Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurological disease caused by HTLV-I infection. It has been shown that HAM/TSP patients have high proviral loads and an extraordinarily high frequency of circulating CD8 + cytotoxic T lymphocytes specific for HTLV-I in their peripheral blood when compared to asymptomatic HTLV-I carriers (AC). We have previously described an intracellular cytokine detection assay, in which interferon-gamma (IFN-gamma) + CD8 + lymphocytes are specific for HTLV-I in infected individuals. Here, we have established a competitive polymerase chain reaction assay to measure the proviral load of patients and investigate a potential relationship between proviral load and virus-specific CD8 + lymphocytes. Genomic DNA was extracted from peripheral blood lymphocytes (PBL) from eight HAM/TSP patients and seven AC for the measurement of HTLV-I measuring proviral loads. The same PBL were analyzed for intracellular IFN-gamma expression by flow cytometry. In the HAM/TSP patients and AC, the average proviral loads were 34,482 and 9784 copy/microg DNA (P = 0.021), and the average of IFN-gamma + CD8 + lymphocytes in total PBL were 1.47 and 0.08% (P = 0.001), respectively. It was confirmed that HAM/TSP patients have both high proviral loads and increased HTLV-I-specific CD8 + lymphocytes. Furthermore, we found a positive correlation between both factors in the patients with HAM/TSP (P = 0.044) but not in the AC (P = 0.508). These findings suggest that the high number of HTLV-I-specific lymphocytes may result from the increased proviral load in HAM/TSP patients.
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Kawanishi
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
authors.forename: A
authors.initials: A
authors.lastname: Manns
authors.forename: S
authors.initials: S
authors.lastname: Jacobson
mesh_terms: D000368:Aged; D016827:CD8 Antigens / Q000097:blood*; D002353:Carrier State / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007425:Intracellular Membranes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000097:blood* / Q000821:virology*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification*; D019562:Viral Load
chemical_list: D016827:CD8 Antigens; D007371:Interferon-gamma