Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan

Kalyanaraman, V. S.; Sarngadharan, M. G.; Nakao, Yoshinobu; Itô, Yôhei; Aoki, Tadao; Gallo, Robert C.

doi:10.1073/pnas.79.5.1653

Cited by 276 publications

(98 citation statements)

References 21 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.

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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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“…HTLV is not an endogenous virus ubiquitous in human germ lines (8) and is readily distinguishable from the known animal retroviruses, including those from subhuman primates (8-10). Antibodies to two HTLV proteins, p24 and p19, have also been found in sera from a few other patients with T-cell malignancies in the United States (11, 12), in a high percentage of patients with adult T-cell leukemias and other leukemias in Japan (13,14), and, more recently, in T-cell malignancies from many other parts of the world (unpublished data).Recently, workers in Japan have also shown that a retrovirus is associated with these diseases in southern Japan (15-17), and we have ascertained that this virus is HTLV (or a closely related strain) (unpublished data). Here we show that HTLV is present in some of the T cells in three independently derived T-cell lines from an infected T-cell lymphoma patient but is not detectable in cultured B cells and other T cells from the same patient.…”

mentioning

confidence: 99%

Human T-cell leukemia-lymphoma virus (HTLV) is in T but not B lymphocytes from a patient with cutaneous T-cell lymphoma.

Gallo¹,

Mann²,

Broder³

et al. 1982

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

138

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A human type C retrovirus, designated HTLV, previously was isolated from or identified in some patients with leukemias and lymphomas of mature T lymphocytes. HTLV is genetically and serologically distinct from any known animal retroviruses. The absence of HTLV proviral sequences in DNA from normal humans showed that HTLV is not a ubiquitous endogenous (germ-line transmitted) virus ofhumans. Antibodies to HTLV core proteins have been identified in some people with T-cell neoplasias and are particularly prevalent in Japanese with adult T-cell leukemia, suggesting that HTLV is acquired horizontally. However, it was possible that HTLV is transmitted through the germ line of some (possibly rare) families and is then expressed in the HTLVpositive malignancies. An opportunity to study this question was provided by the development of several T-cell lines and a B-cell line from one HTLV-positive patient with a cutaneous T-cell lymphoma. Here we report that HTLV proteins or nucleic acids (or both) are found in three independently derived T-cell lines, all shown by HLA typing to have originated from the patient. In contrast, the B-cell line, the identity of which was also ascertained by HLA typing, contained no detectable HTLV protein, RNA, or proviral DNA. Because the sensitivity of the latter assay is more than sufficient to detect one proviral equivalent per haploid genome, the results indicate that HTLV was not transmitted to this patient through the germ line but rather was acquired by infection.The discovery (1,2) and purification (3) of T-cell growth factor (TCGF) has made it possible to grow relatively mature human T cells from normal (1, 2) and neoplastic (4) sources routinely in liquid suspension culture for long periods. We have identified a human type C retrovirus in cultured T cells from several patients with leukemia-lymphoma. of relatively mature T cells. In some instances, the virus (called HTLV) has been constantly produced by these T cells (5, 6) which have become independent of TCGF and established as permanent cell lines, apparently because of eventual constitutive release of TCGF (7). In two instances, the virus has been characterized in detail (5, 6). HTLV is not an endogenous virus ubiquitous in human germ lines (8) and is readily distinguishable from the known animal retroviruses, including those from subhuman primates (8-10). Antibodies to two HTLV proteins, p24 and p19, have also been found in sera from a few other patients with T-cell malignancies in the United States (11, 12), in a high percentage of patients with adult T-cell leukemias and other leukemias in Japan (13,14), and, more recently, in T-cell malignancies from many other parts of the world (unpublished data).Recently, workers in Japan have also shown that a retrovirus is associated with these diseases in southern Japan (15-17), and we have ascertained that this virus is HTLV (or a closely related strain) (unpublished data). Here we show that HTLV is present in some of the T cells in three independently derived T-cell lines fr...

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“…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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Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan

Cited by 276 publications

References 21 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.

Human T-cell leukemia-lymphoma virus (HTLV) is in T but not B lymphocytes from a patient with cutaneous T-cell lymphoma.

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

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