Green tea polyphenols (TEA) are known to exhibit antioxidative activity as well as tumor-suppressing activity. In order to examine the tumor-suppressing activity of TEA against adult T-cell leukemia (ATL), we cultivated peripheral blood T lymphocytes of ATL patients (ATL PBLs), an HTLV-I-infected T-cell line (KODV) and healthy controls (normal PBLs) for 3 days in the presence of TEA and its main constituent, epigallocatechin-3-gallate (EGCg), to measure cell proliferation and apoptosis, and to quantitate mRNAs of HTLV-I pX and β β β β-actin genes of the cultured cells. Growth of ATL

Human T-cell lymphotropic virus type 1 is vertically transmitted in neonatal life and is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in adults. Persistence of HTLV-1 in host T cells, clonal expansion of the HTLV-1 carrying T cells, and emergence of malignantly transformed T cells are in accord with the multistep model of human cancer and roles for continuous interaction between host genes and environmental factors. This article reviews two lines of HTLV-1 investigation, one regarding worldwide surveillance of HTLV-1 infection foci by serological testing and molecular analysis of HTLV-1 isolates, and the other focusing on genetics of the human leukocyte antigen (HLA) that determines the ethnic background of HTLV-1 permissiveness and susceptibility to ATL or HAM/TSP. The serological surveillance revealed transcontinental dispersal of HTLV-1 in the prehistoric era that started out of Africa, spread to Austro-Melanesia and the Asian continent, then moved to North America and through to the southern edge of South America. This was highlighted by an Andean mummy study that proved ancient migration of paleo-mongoloid HTLV-1 from Asia to South America. Phylogenetic analysis of HLA alleles provided a basis for ethnic susceptibility to HTLV-1 infection and associated diseases, both ATL and HAM/TSP. Ethnicity-based sampling of peripheral blood lymphocytes has great potential for genome-wide association studies to illuminate ethnically defined host factors for viral oncogenesis with reference to HTLV-1 and other pathogenic elements causatively associated with chronic disease and malignancies. (Cancer Sci 2011; 102: 295-301) Ethnoepidemiology of HTLV-1 is a new paradigm in cancer research C ancer is caused by chronic stimuli by chemical, physical, and biological agents (1)(2)(3)(4) which interact with the internal tissue milieu of the human body. Human T-cell lymphotropic virus type 1 (5) is an oncornavirus that causes the T cell malignancy known as adult T cell leukemia (ATL) in a subgroup of HTLV-1 infected people.(6-9) It also gives rise to neurological, ophthalmological, and dermatological disorders called HTLV-1-associated myelopathy ⁄ tropical spastic paraparesis (HAM ⁄ TSP), HTLV-1 uveitis, and infective dermatitis in other groups of HTLV-1 infection. (10)(11)(12) Here is an intriguing paradox in that one pathogen (HTLV-1) causes two diseases (ATL and HAM ⁄ TSP), contradicting the classical theory of medical microbiology (Koch's postulate of one pathogen, one disease). We thus hypothesized the presence of host factor(s) relevant to HTLV-1 permissiveness and disease susceptibility that are determined by the genetic background of HTLV-1 infected people of different ethnic groups. (13,14) Molecular studies have revealed that 5¢-LTR genes of HTLV-1 regulate encoding of Tax ⁄ Rex proteins that are responsible for HTLV-1 transactivation, (15) whereas 3¢-LTR genes encode HTLV-1 basic leucine zipper (HBZ) proteins essential for maintenance ...

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Human T‐lymphotropic virus‐I (HTLV‐I) causes adult T‐cell leukemia/lymphoma (ATL) and HTLV‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). We postulated a higher disease risk for people with common human leukocyte antigen (HLA) types, due to a narrower immune response against viral or neoplastic antigens, compared to people with uncommon types. HLA class‐I (A,B) and class‐II (DRB1, DQB1) allele and haplotype frequencies in 56 ATL patients, 59 HAM/TSP patients and 190 population‐based, asymptomatic HTLV‐I‐infected carriers were compared by logistic regression overall (score test) and with odds ratios (ORs) for common types (prevalence >50% of asymptomatic carriers) and by prevalence quartile. HTLV‐I proviral load between asymptomatic carriers with common versus uncommon types was compared by t‐test. ATL differed from asymptomatic carriers in overall DQB1 allele and class‐I haplotype frequencies (p ≤≤ 0.04). ATL risk was increased significantly with common HLA‐B (OR 2.25, 95% CI 1.19–4.25) and DRB1 (OR 2.11, 95% CI 1.13–3.40) alleles. Higher prevalence HLA‐B alleles were associated with higher ATL risk (OR 1.14 per quartile, ptrend = 0.02). Asymptomatic carriers with common HLA‐B alleles had marginally higher HTLV‐I proviral load (p = 0.057). HAM/TSP risk did not differ consistently with common HLA types. Thus, ATL risk, but not HAM/TSP risk, was increased with higher prevalence HLA‐B alleles. Perhaps breadth of cellular immunity affects risk of this viral leukemia/lymphoma. © 2007 Wiley‐Liss, Inc.

RESUMENLos antígenos leucocitarios (HLA) están vinculados por genes altamente polimórficos, con el complejo mayor de histocompatibilidad localizando en el brazo corto del cromosoma 6. Dos contingentes distin tos del gen del HLA se heredan de los padres en forma mendeliana y que se expresan codominantemente para producir dos sets de antígenos de HLA: A, B-C, DR y DQ, así como los fenotipos comple mentarios. El tipo de HLA y los haplotipos son útiles para la identificación individual y/o grupos genéticos en los seres humanos. Otra importante función de la diversidad del HLA es el reconocimiento inmunológico de los antígenos propios o ajenos. Los autoantígenos originados en células autólogas y los antígenos de origen exógenos son procesados en proteosomas para degradarlos a fragmentos peptídicos los que encajan especialmente de acuerdo a la particular configuración de las moléculas de HLA.Los complejos HLA peptídicos son reconocidos por un repertorio de linfocitos T o B que expresan una respuesta inmune específica.Las células T y B que reconocen antígenos autólogos son naturalmente destruidas, mientras que aquellas células expuestas a los antígenos exógenos sobrevi ven largamente y producen una respuesta amnéstica contra los mismos antígenos. Algunas células T pueden sobrevivir más de 30 años. Así, la memoria inmune a las células T o B es útil para la búsqueda de antiguas epidemias de enfermedades infecciosas sobrepasada por los distintos grupos étnicos. En ese sentido el estudio de HLA entre los andinos, así como los antecedentes que se refieren a su suscepti bilidad por las infecciones por HTLV 1 son semejan tes a las que expresan los japoneses del sur.