Natural Antibodies to Human Retrovirus HTLV in a Cluster of Japanese Patients with Adult T Cell Leukemia

Robert-Guroff, Marjorie; Nakao, Yoshinobu; Notake, Kunihiro; Itô, Yôhei; Sliski, Ann; Gallo, Robert C.

doi:10.1126/science.6760397

Cited by 345 publications

(112 citation statements)

References 17 publications

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“…The observations that anti-pl9 + thymic epithelium is HTLV p24 negative, that no HTLV proviral DNA sequences can be detected with HTLV c-DNA probes by Southern blot hybridization techniques, and that all thymus tissues tested from donors older than 8 wk gestation were anti-pl9 + provide strong evidence against this. Moreover, epidemiologic data strongly suggest that HTLV-associated Tcell leukemia is horizontally passed as an infectious disease and not by vertical transmission (4)(5)(6)(7)(8)(9). Molecular hybridization studies have verified this and proven that the infection is postzygotic (3,21).…”

Section: Discussionmentioning

confidence: 81%

Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny.

Haynes¹,

Robert-Guroff²,

Metzgar³

et al. 1983

The Journal of Experimental Medicine

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Using monoclonal antibody 12/1-2 against a 19,000-dalton human T cell leukemia virus (HTLV) protein (anti-p19), previously demonstrated to be reactive with HTLV-infected human cells, but not in numerous other uninfected cells, we found a reactive antigen to be expressed on the neuroendocrine component of human thymic epithelial cells but not on any other normal epithelial or neuroendocrine human tissues. Moreover, this reactive antigen is acquired on neuroendocrine thymic epithelium during thymic ontogeny--first appearing on fetal thymic epithelial cells between 8 and 15 wk gestation. While only a portion of thymic epithelial cells in the subcapsular cortical region of 15- and 24-wk fetal thymuses contained anti-p19+ epithelial cells, the entire subcapsular cortical region of newborn thymus epithelium was anti-p19+. By age 3 yr, normal subjects' entire subcapsular cortical and medullary thymic epithelium was anti-p19+. Using antibody against HTLV core protein, p24, and c-DNA probes for HTLV DNA, neither HTLV-specific p24 protein nor proviral DNA could be demonstrated in anti-p19+ thymic epithelial tissue. However, thymic epithelial extracts, disrupted HTLV extracts, as well as purified HTLV p19 antigen all inhibited the binding of anti-p19 antibody to thymic epithelium. Thus, anti-p19 may recognize a determinant on an HTLV-encoded 19,000-dalton structural protein that is shared by human thymic epithelium. Alternatively, anti-p19 defines a host encoded protein that is selectively expressed by normal thymic epithelium, and is induced to be expressed in HTLV-infected malignant T cells.

show abstract

Section: Discussionmentioning

confidence: 81%

Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny.

Haynes¹,

Robert-Guroff²,

Metzgar³

et al. 1983

The Journal of Experimental Medicine

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“…The number of syncytia decreased gradually with increase in cell passages. Thus, most of these syn- (5,10,13,35,36). Therefore, we next examined whether syncytia formation was neutralized by these antibodies.…”

Section: Methodsmentioning

confidence: 99%

“…HTLV has also been detected in patients from different parts of the world (11). Although the geographical and racial distributions of HTLV-i.e., HTLV-Iand ATL virus were quite different, these two viruses are closely related or identical (12)(13)(14). Another HTLV, HTLV-II, was isolated from a patient with hairy cell leukemia of T-cell origin (15).…”

mentioning

confidence: 99%

Detection of lymphocytes producing a human retrovirus associated with adult T-cell leukemia by syncytia induction assay.

Hoshino¹,

Shimoyama²,

Misawa³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

119

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Recently 10 T-cell lines were established from patients with adult T-cell leukemia (ATL). During establishment of these cell lines, it was found that when T-cell lines expressing the ATL-associated retroviral antigen were cocultivated with 8C cat cells, multinucleated syncytia were formed. Retroviral antigen-negative T-cell lines did not induce syncytia. Peripheral blood lymphocytes obtained from ATL patients did not express the retroviral antigen before cultivation in vitro but became positive for the retroviral antigen after cultivation for a short period; these retroviral antigen-positive lymphocytes, but not retroviral antigen-negative lymphocytes, induced syncytia upon cocultivation with 8C cells. Peripheral blood lymphocytes isolated from patients with chronic lymphocytic leukemia of T-cell origin or Skzary syndrome or from normal adults and lymph node cells from a patient with immunoblastic lymphadenopathy-like T-cell lymphoma did not express the retroviral antigen even after cultivation in vitro and did not induce syncytia upon cocultivation with SC cells. Thus, there was complete agreement between the presence of the retroviral antigen in established T-cell lines or freshly isolated peripheral blood lymphocytes and their ability to induce syncytia. Syncytia formation was enhanced 5-to 20-fold by the presence of Polybrene and inhibited by addition of plasma of ATL patients to the cocultures. Syncytia were detected within 4 hr on cocultivation of 8C cells with the retroviral antigen-positive T-cells, indicating that most syncytia were formed by early polykaryocytosis. After cocultivation, a clone of 8C cells that harbored the AU virus genome and had syncytia-inducing activity was isolated. These findings indicate that the retrovirus associated with AU has syncytiainducing activity. Syncytia induction assay using 8C cells will be useful for detection and characterization of human retrovirus associated with T-cell malignancies.

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“…These regions were the Caribbean [5] and southwestern Japan [51]. The 318 disease in the Caribbean was called lymphosarcoma cell leukemia, and that in Japan was called adult T cell leukemia; both were found to be closely associated with the presence of HTLV-I by seroepidemiology [3, 13,39]. Both diseases are now regarded as the same clinical entity, and are collectively called adult T cell leukemia/lymphoma (A TLL).…”

Section: B Htl V -I and Adult T Cell Leukemia/ Lymphomamentioning

confidence: 99%

The Human T-Cell Leukemia Virus Family, Adult T Cell Leukemia, and AIDS

Gallo¹,

Sarngadharan²,

Popovič³

et al. 1985

Modern Trends in Human Leukemia VI New Results in Clinical and Biological Research Including Pediatric Oncology

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Natural Antibodies to Human Retrovirus HTLV in a Cluster of Japanese Patients with Adult T Cell Leukemia

Cited by 345 publications

References 17 publications

Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny.

Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny.

Detection of lymphocytes producing a human retrovirus associated with adult T-cell leukemia by syncytia induction assay.

The Human T-Cell Leukemia Virus Family, Adult T Cell Leukemia, and AIDS

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