Comparative evaluation of new and conventional classifications of magnifying endoscopy with narrow band imaging for invasion depth of superficial esophageal squamous cell carcinoma.

A new classification of magnifying endoscopy with narrow band imaging (ME-NBI) for diagnosing and staging superficial esophageal squamous cell carcinoma (SESCC) was proposed by the Japan Esophageal Society in 2011. This study aimed to compare the new classification with the conventional classifications (Inoue's classification and Arima's classification). This was a prospective analysis of data from a single cancer center involving 151 consecutive patients with 156 SESCCs that were endoscopically or surgically resected. Initially, only ME-NBI images were selected and reviewed independently by three experienced endoscopists. White light imaging (WLI) was then evaluated separately after an interval. The diagnostic performance of each classification and interobserver agreement were assessed, and the WLI findings that affect the diagnosis by the new classification were identified. The specificity for classifying invasive depth as epithelium (EP)/lamina propria mucosae (LPM) confined was higher with the new classification than with Inoue's classification (0.512 vs. 0.349; P = 0.02) and Arima's classification (0.512 vs. 0.279; P < 0.01). However, the sensitivity was lower (0.902 vs. 1.000; P < 0.01) compared with Arima's classification. The concordance rates of three evaluators (κ values) were 0.52 for the new classification, 0.50 for Inoue's classification, and 0.23 for Arima's classification. On multivariate analysis, thickness on WLI independently affected the accuracy of diagnosis with the new classification (OR 3.23; 95%CI, 1.30-8.03). The new classification is superior to conventional classifications with respect to specificity for diagnosing SESCC with depth EP/LPM. Thickness on WLI was a factor negatively affecting the diagnostic performance of the new classification.

Subaru telescope observations of Deep Impact.

The impact cratering process on a comet is controversial but holds the key for interpreting observations of the Deep Impact collision with comet 9P/Tempel 1. Mid-infrared data from the Cooled Mid-Infrared Camera and Spectrometer (COMICS) of the Subaru Telescope indicate that the large-scale dust plume ejected by the impact contained a large mass (approximately 10(6) kilograms) of dust and formed two wings approximately +/-45 degrees from the symmetric center, both consistent with gravity as the primary control on the impact and its immediate aftermath. The dust distribution in the inner part of the plume, however, is inconsistent with a pure gravity control and implies that evaporation and expansion of volatiles accelerated dust.

Evaluation of bedmaking-related airborne and surface methicillin-resistant Staphylococcus aureus contamination.

The number of airborne methicillin-resistant Staphylococcus aureus (MRSA) before, during and after bedmaking was investigated. Air was sampled with an Andersen air sampler in the rooms of 13 inpatients with MRSA infection or colonization. Sampling of surfaces, including floors and bedsheets, was performed by stamp methods. MRSA-containing particles were isolated on all the sampler stages-stage 1 (>7 microm diameter) to stage 6 (0.65-1.1 microm). The MRSA-containing particles were mostly 2-3 microm diameter before bedmaking and >5 microm during bedmaking. The number was significantly higher 15 min after bedmaking than during the resting period, but the differences in counts after 30 and 60 min were not significant. MRSA was detected on many surfaces. The results suggest that MRSA was recirculated in the air, especially after movement. To prevent airborne transmission, healthcare staff should exercise great care to disinfect inanimate environments. Further studies will be needed to confirm the level of MRSA contamination of air during bedmaking and establish measures for prevention of airborne transmission.

[Clinical significance of the Streptococcus milleri group in peritonsillar abscesses].

Few researchers have microbiologically studied peritonsillar abscesses in detail, and their results have been conflicting. Although Streptococcus pyogenes (Group A beta-streptococcus) is commonly considered an important pathogen in this infection, recent studies have demonstrated the recovery of many other streptococci mainly consisting of alpha-streptococci. Few studies have identified these streptococci at the species level, however. We studied details of bacteriology in 31 cases of peritonsillar abscess treated between 1991 and 2000. The Streptococcus milleri group was most frequently isolated (25.8%), followed by Eikenella corrodens (9.7%), Staphylococcus aureus (6.5%), and S. pyogenes (3.2%). The S. milleri group, consisting of 3 species of Streptococcus constellatus, S. intermedius, and S. anginosus, forms part of the normal flora most commonly found in the mouth, throat, gastrointestinal tract, and genital tract. These species have become known as an important pathogen in abscess disease but little attention has been paid to their role in peritonsillar abscesses. To adequately culture the S. milleri group, incubation in air containing carbon dioxide or in an anaerobic condition is required, and then the differentiation of the 3 species requires the biochemical reactivity tests. Since hemolytic patterns of the S. milleri group vary, we studied the population of alpha-, beta-, and gamma-hemolytic strains among 36 strains of this group. We found 32 (88.8%) to be alpha-hemolytic. Although not all alpha-hemolytic strains belong to the S. milleri group, a considerable number of this group could be missed among alpha-streptococci isolated from the peritonsillar abscess. As antibiotics began being used widely, normal flora such as the S. milleri group may have become an important pathogen in peritonsillar abscesses due to an imbalance between organisms and host defense.

HLA-A*26, HLA-B*4002, HLA-B*4006, and HLA-B*4801 alleles predispose to adult T cell leukemia: the limited recognition of HTLV type 1 tax peptide anchor motifs and epitopes to generate anti-HTLV type 1 tax CD8(+) cytotoxic T lymphocytes.

Genetic risk for adult T cell leukemia (ATL) has been implicated by ethnic and familial segregation of ATL patients from HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). To clarify the genetic risk for ATL, we characterized HLA class I alleles of ATL patients and analyzed the anchor motifs of HTLV-1 peptides binding to HLA class I molecules, using 291 lines of anti-HTLV-1 CD8(+) cytotoxic T lymphocytes (CTLs) generated in vitro with a total of 165 synthetic peptides for HTLV-1 Tax and Env proteins. Allele frequencies of HLA-A*26, B*4002, B*4006, and B*4801 were significantly higher in ATL patients than in HAM/TSP patients and asymptomatic HTLV-1 carriers in southern Japan. CD8(+) CTL analysis revealed the HTLV-1 Tax peptide sequence to completely lack anchor motifs of peptides binding to HLA-A*26,B*4002, and B*4006 molecules but to possess one anchor for HLA-B*4801, while the HTLV-1 Env peptide sequence had many anchor motifs for HLA-A*26, B*4002, B*4006, and B*4801 molecules. Most ATL patients featured heterozygous HLA class I alleles composed of HLA-A*26, B*4002, B*4006, and B*4801, with a lower number of HTLV-1 Tax peptide anchor motifs and epitopes generating anti-HTLV-1 Tax CD8(+) CTLs than individuals possessing other HLA alleles. The relationship between Tax epitope and ATL incidence was verified by the significantly decreased number of HTLV-1 Tax epitopes in ATL patients compared with asymptomatic HTLV-1 carriers (p < 0.01) as well as late onset ATL patients (p < 0.001). These results indicate that HLA-A*26, B*4002, B*4006, and B*4801 alleles predispose to ATL because of the limited recognition of HTLV-1 Tax peptide anchor motifs and epitopes capable of generating anti-HTLV-1 Tax CD8(+) CTLs.

Human leukocyte antigens related to Epstein-Barr virus-associated gastric carcinoma in Japanese patients.

To assess the association between specific types of human leukocyte antigen and the risk of Epstein-Barr virus (EBV)-associated gastric carcinoma, serological typing for major histocompatibility complex class I and class II antigens was performed for 110 EBV-positive and 155 EBV-negative gastric carcinoma cases. In class I analysis, the frequency of B59 in the EBV-positive cases was higher than for the EBV-negative cases (odds ratio (OR) 3.06; 95% confidence interval (CI) 1.02-9.23). For class II antigens, DQ3 and DR9 frequencies in the EBV-positive cases were higher (OR 1.94; 95% CI 1.16-3.24 and OR 1.93; 95% CI 1.11-3.37, respectively), whereas DR11 frequency was lower than found in the EBV-negative cases (OR 0.10; 95% CI 0.01-0.79). After adjusting for multiple comparisons, only DR11 frequency remained significantly lower in the EBV-positive cases (P = 0.04), and the association of DQ3 was marginally significant (P = 0.05). These results suggest that the presence of DR11-restricted cytotoxic T cells (CTLs) related to EBV-associated gastric carcinoma, or a deficiency of DR11 and a high frequency of DQ3 may be genetic markers for a population at greater risk of EBV-associated gastric carcinoma. However, further extensive studies to more cases and DNA typing are needed because our findings in this study are exploratory.

[Clinical and bacteriological significance of the Streptococcus milleri group in deep neck abscesses].

Streptococcus constellatus, S. intermedius, and S. anginosus, the three species of the S. milleri group, form part of the normal flora most commonly found in the mouth, throat, gastrointenstinal tract, and genital tract. The S. milleri group has become known as an important pathogen in abscess disease, but little attention has been paid to their role in deep neck abscesses. We have treated 9 patients with deep neck abscesses relating to the S. milleri group since 1991, and regarded this group as an important pathogen also in these abscesses. We studied the frequency of the S. milleri group isolated from deep neck abscesses in our cases and from the literature and discuss clinical significance and bacteriological pathogenesis. Cases numbered 27 treated at our facility since 1991 and 200 cases reported in the Japanese literature since 1990. Of our 9 cases, 4 originated from acute pharyngitis, 3 from peritonsillar abscesses, and 2 from odontogenic infection. Serious complications such as mediastinitis, cervical necrotizing fasciitis, sepsis accompanied by disseminated intravascular coagulation, and spondylitis of the cervical vertebrae were seen in 4 cases. Among organisms isolated, the S. milleri group appeared to be a pathogen contributing to abscess formation and to serious complications. The genus Streptococcus was most frequently isolated both in our 27 cases (66.7%) and the 200 in the literature (45.5%). Among species of the genus Streptococcus, the S. milleri group numbered the highest in our cases at 33.3% but only 8.5% in the literature. Cases in the literature, however, contained many unknown species of Streptococci--31.5% vs. 18.5% in our cases. alpha-streptococcus was frequently reported in the literature among unknown species of Streptococci--36 of 63. Culture-negative cases were also numbered more in the literature than in our case--29.0% vs. 18.5%. Special conditions and procedures are required to suitably isolate and detect the S. milleri group. Since not all facilities use identical techniques in routine bacteriological examination, a considerable number of the S. milleri group could be missed in unknown species of Streptococci or alpha-streptococcus and culture-negative cases. The detailed pathogenesis of the S. milleri group remains to be clarified. Infection by normal flora on mucosa is thought to occur due to an imbalance between organisms and host defense in deep neck abscesses. Some strains of the S. milleri group have been reported to produce many tissue-destroying enzymes such as collagenase and hyaluronidase. The co-existence of the S. milleri group with some anaerobe strains has also been suggested to accelerate inflammation. We discuss the mechanism inducing the massive release of cytokines through T cell response to certain exotoxins produced by S. milleri group, as reported in toxic shock-like syndrome due to the group A beta-streptococcus and in alpha-streptococcal shock syndrome due to viridans streptococci (alpha-streptococci).

[A case of chronic masticator space abscess].

Different neoplasms and infections are known to involve the masticator space, but pathological diagnosis and treatment of these lesions are not always simple due to anatomical complexity. We treated a 66-year-old man with an abscess in the nasopharyngeal masticator space. Physical and CT findings resembled those of neoplastic lesion because the onset dated back 5 years and the patient was lacking in notable signs of infection. Surgery through the maxillary sinus to the lesion enabled us to confirm its pathology and drain pus, with subsequent cure. We noted periodontal infection of the mandibular molars accompanied with osteomyelitis as a cause of this abscess, so infected molars were extracted 13 days after surgery. The infection had spread upward along the mastication muscles, resulting in an abscess in both the upper masseter muscle and the lower temporalis muscle. Based on a review of the literature, most abscesses in the masticator space originate from the mandibular molar, while the most impressive physical finding varied between the submandibular region and temporal fossa, as did its acute or chronic clinical course. Such clinical manifestations appear to reflect the pattern of infection spread along the muscles of mastication and a pattern involving adjacent spaces. We emphasize diagnostic significance when assessing findings for each mastication muscle and mandibular bone depicted using computed tomography, magnetic resonance imaging, and bone-scan technetium.

Green tea polyphenols induce apoptosis in vitro in peripheral blood T lymphocytes of adult T-cell leukemia patients.

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 beta-actin genes of the cultured cells. Growth of ATL PBLs was significantly inhibited by 9-27 microg/ml of TEA and EGCg, in contrast to minimal growth inhibition of T cells of normal PBLs. Inhibition of KODV was intermediate between ATL PBLs and normal PBLs. The ATL PBLs and KODV treated with 27 microg/ml of either TEA or EGCg induced apoptotic DNA fragmentation, producing terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells, while the normal PBLs treated with the same concentration of TEA or EGCg produced a negligibly small number of TUNEL-positive cells, in which apoptotic DNA fragmentation was not detectable. Expression of HTLV-I pX mRNA was suppressed more than 90% in ATL PBLs by treatment with 3-27 microg/ml of either TEA or EGCg, while expression of beta-actin mRNA was much less suppressed by treatment with the same concentration of TEA or EGCg. These results indicate that TEA and EGCg inhibit growth of ATL PBLs, as well as HTLV-I-infected T-cells, by suppressing HTLV-I pX gene expression and inducing apoptotic cell death.

The presence of ancient human T-cell lymphotropic virus type I provirus DNA in an Andean mummy.

The worldwide geographic and ethnic clustering of patients with diseases related to human T-cell lymphotropic virus type I (HTLV-I) may be explained by the natural history of HTLV-I infection. The genetic characteristics of indigenous people in the Andes are similar to those of the Japanese, and HTLV-I is generally detected in both groups. To clarify the common origin of HTLV-I in Asia and the Andes, we analyzed HTLV-I provirus DNA from Andean mummies about 1,500 years old. Two of 104 mummy bone marrow specimens yielded a band of human beta-globin gene DNA 110 base pairs in length, and one of these two produced bands of HTLV-I-pX (open reading frame encoding p40x, p27x) and HTLV-I-LTR (long terminal repeat) gene DNA 159 base pairs and 157 base pairs in length, respectively. The nucleotide sequences of ancient HTLV-I-pX and HTLV-I-LTR clones isolated from mummy bone marrow were similar to those in contemporary Andeans and Japanese, although there was microheterogeneity in the sequences of some mummy DNA clones. This result provides evidence that HTLV-I was carried with ancient Mongoloids to the Andes before the Colonial era. Analysis of ancient HTLV-I sequences could be a useful tool for studying the history of human retroviral infection as well as human prehistoric migration.

Activation of protein kinase B induced by H(2)O(2) and heat shock through distinct mechanisms dependent and independent of phosphatidylinositol 3-kinase.

Protein kinase B (PKB) is a downstream target of phosphatidylinositol (PI) 3-kinase in the signaling pathway of growth factors, and is activated by cellular stress such as H(2)O(2) and heat shock. To study the mechanism of the stress-induced activation of PKB, PI 3-kinase products were measured in stress-stimulated cells. Both PI 3,4-bisphosphate and PI 3,4, 5-trisphosphate increased in H(2)O(2)-treated cells, and the elevation of these phospholipids and activation of PKB were concurrently blocked by wortmannin, a potent inhibitor of PI 3-kinase. In heat-shocked cells, the level of PI 3,4-bisphosphate did not change while that of PI 3,4,5-trisphosphate increased slightly, and an association between PKB molecules was observed. Two active PKB fractions, presumably monomeric and oligomeric forms, were resolved from heat-shocked cells by gel filtration column chromatography. Activation of the former was suppressed by pretreatment with wortmannin, whereas the generation and activation of the latter were not blocked by the PI 3-kinase inhibitor. Only the monomeric form, but not the oligomeric form, was recovered from H(2)O(2)-treated cells, and its activation was prevented by wortmannin. These results indicate that PKB is activated by two distinct mechanisms that are dependent and independent of PI 3-kinase in stress-stimulated cells.

Characteristic distribution of HTLV type I and HTLV type II carriers among native ethnic groups in South America.

To confirm the geographic and ethnic segregation of HTLV-I and HTLV-II carriers in native populations in South America, we have conducted a seroepidemiological study of native populations in South America, including HTLV-I carriers distributed among seven ethnic groups in the Andes highlands of Colombia, Peru, Bolivia, Argentina, and Chile, and two ethnic groups on Chiloe Island and Easter Island; and HTLV-II carriers distributed among seven ethnic groups of the lowlands along the Atlantic coast of Colombia, Orinoco, Amazon, and Patagonia, and one ethnic group on Chiloe Island. The incidence rate of HTLV-I and HTLV-II carriers varied among the ethnic groups, ranging from 0.8 to 6.8% for HTLV-I seropositivity and from 1.4 to 57.9% for HTLV-II seropositivity. A new HTLV-I focus was found among the Peruvian Aymara (1.6%), the Bolivian Aymara (5.3%) and Quechua (4.5%), the Argentine Puna (2.3%), and the Chilean Atacama (4.1%), while on HTLV-II focus was found among the Brazilian Kayapo (57.9%), the Paraguayan Chaco (16.4%), and the Chilean Alacalf (34.8%) and Yahgan (9.1%). The distribution of HTLV-I/II foci showed a geographic clustering of HTLV-I foci in the Andes highlands and of HTLV-II foci in the lowlands of South America. It was thus suggested that South American natives might be divided into two major ethnic groups by HTLV-I and HTLV-II carrier state.

Expression of heat shock protein 70 mRNA in polymorphonuclear cells responding to surgical stress.

PURPOSE: This study was performed to investigate the expression of heat shock protein (HSP) 70 mRNA in polymorphonuclear neutrophils (PMN) as a possible new biomarker for surgical stress. METHODS: The HSP70 mRNA in PMN of 10 patients who underwent lobectomy was evaluated by Northern blot analysis. Their leukocyte counts, including white blood cells (WBC) and PMN, plasma cortisol levels, and plasma interleukin-6 (IL-6) levels, were obtained by cell counting, radioimmunoassay, and enzyme-linked immunosorbent assay, respectively. RESULTS: The level of HSP70 mRNA in PMN slightly increased at the end of surgery and showed a significant increase 6 h after surgery. It promptly decreased at 24 h postoperatively and returned to the basal preanesthetic level 48 h after surgery. On the other hand, WBC/PMN counts, plasma cortisol, and IL-6 significantly increased at the end of surgery. WBC/PMN counts remained at increased levels until 48 h postoperatively. Cortisol peaked at 6 h postoperatively and gradually decreased. IL-6 reached a maximum at 1 h postoperatively, then tapered down to its basal level at 48 h postoperatively. CONCLUSION: Expression of HSP70 mRNA in PMN that is induced after thoracic surgery appears to be a promising candidate as a marker for evaluating surgical stress.

HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia.

The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRB1*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.

Induction of cyclooxygenase-2 causes an enhancement of writhing response in mice.

Pretreatment of mice with lipopolysaccharide for 16 h enhanced the number of acetic acid-induced writhing reactions by 2 to 3-fold. In the peritoneal exudates at 10 min after acetic acid injection, 6-keto-prostaglandin F1alpha was detected as a major prostanoid, and this level increased by several-fold by the pretreatment with lipopolysaccharide. The writhing reaction and the prostaglandin formation were almost completely suppressed by indomethacin. However, the lipopolysaccharide-induced enhancement of writhing reaction and an increment of 6-keto-prostaglandin F1alpha level were diminished by the administration of cyclooxygenase-2-selective inhibitors, such as NS-398, nimesulide, or L-745337, to a level similar to the mice that did not receive lipopolysaccharide. Cyclooxygenase-2 protein in the exudates became detectable at 5-48 h after the lipopolysaccharide-pretreatment. These results suggest that the increased prostaglandin production by cyclooxygenase-2 could be responsible for enhancement of the acetic acid-induced writhing reaction by lipopolysaccharide pretreatment.

Human leukocyte antigen class II alleles associated with human T-cell lymphotropic virus type I infection and adult T-cell leukemia/lymphoma in a Black population.

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I-related diseases. METHODS: We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51). All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reaction-based methods to examine HLA class II DRB1 and DQB1 alleles. RESULTS: Two antigens determined by serotyping, DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42% versus 22% for DR15 [odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.0-7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP. CONCLUSIONS: These data suggest that host genetic background is an important factor in determining whether HTLV-I carriers develop either ATL or HAM/TSP.

An expression of anaplastic large cell lymphoma-associated antigens on HTLV-I-infected CD4+ T cells.

We investigated tumor-associated antigens induced by infection with human T-lymphotropic virus type I(HTLV-I). Anaplastic large cell lymphoma (APLL) antigens were found to be expressed on interleukin 2 (IL-2)-dependent, HTLV-I-infected CD4+ T-cell lines established from patients with adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. However, APLL antigens were not detected on unstimulated lymphocytes, mitogen-activated T lymphocytes, or Epstein-Barr virus-infected B cells. Furthermore, APLL antigens were not found on IL-2-independent HTLV-I-transformed cells such as MT-I or MT-2. When naive CD4+ T cells were infected with HTLV-I in vitro in the presence of IL-2, the APLL antigens were detected on them 4 weeks after infection. The expression level increased in a time-dependent fashion. These results indicate that HTLV-I infection induces a unique category of tumor-associated antigens on CD4+ T cells.

Human CD4+ T lymphocytes recognize a highly conserved epitope of human T lymphotropic virus type 1 (HTLV-1) env gp21 restricted by HLA DRB1*0101.

HTLV-1 causes two distinct human diseases, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukaemia/lymphoma (ATL). Persistently infected individuals carry a risk of <1% of developing either disease. These basic epidemiological data imply that virus-host interactions, especially immunogenetic factors, influence the outcome of infection. Several studies showed that the HLA class II DR1 DQ5 haplotype is over-represented in HAM/TSP, but rare in ATL. Therefore, we selected four patients with HAM/TSP and one seronegative control who all carried the HLA DR1 DQ5 haplotype. We analysed the CD4+ T lymphocyte response against eight synthetic peptides of HTLV-1 envelope (env) glycoprotein gp21, a crucial target antigen in HAM/TSP. The first of two immunodominant epitopes corresponded to a domain of the HTLV-1 envelope protein which had previously been shown to be essential for HTLV-1 envelope function. The second immunodominant epitope overlapped a highly conserved sequence of the retroviral transmembrane envelope protein. DR1 (DRB1*0101)-restricted T lymphocytes were activated by the conserved peptide sequence in nanomolar concentrations. In contrast, this conserved sequence can also induce non-specific, cAMP-mediated immunosuppressive effects on T cells when added in micromolar concentrations to culture media, as shown by Haraguchi S, Good RA, James-Yarish M, Cianciolo GJ, Day NK, Proc Natl Acad Sci USA 1995; 92:5568-71. Hence, HTLV-1 env gp21 might exert either stimulating immunological or immunosuppressive effects in HTLV-1-infected individuals, depending on the level of its expression and the presence of HLA DRB1*0101.