Large granular lymphocyte (LGL) lymphoproliferative diseases: Naturally cytotoxic tumors in man and experimental animals

Reynolds, Craig W.

doi:10.1016/s1040-8428(85)80002-0

Cited by 8 publications

(6 citation statements)

References 99 publications

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“…These cells may mediate a similar function in vivo, thereby providing a cytotoxic T lymphocyte with the capacity to recognize and lyse an antibody-coated target through a structure distinct from the T cell antigen receptor. Although there have been reports (15,16) that T cells isolated from patients with certain lymphoproliferative disorders can mediate ADCC, but not NK activity, the isolation of this T cell subset from the peripheral blood of a normal, healthy individual has not been reported. As previously demonstrated for CD3-,CD16 + NK cells (13), the CD3+,CD16 + T cells preferentially mediate ADCC with IgG2a antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…from peripheral blood, concanavalin A-activated cultures, or mixed lymphocyte response cultures. However, several patients with T cell lymphoproliferative disorders have been shown (14)(15)(16)(17) to coexpress both CD3 antigen and IgG FcR. This finding prompted us to investigate whether or not any CD3 ÷ T lymphocytes obtained from normal individuals express the IgG FcR detected by the anti-Leu-11 mAb.…”

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confidence: 99%

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Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).

Lanier¹,

Kipps²,

Phillips³

1985

The Journal of Experimental Medicine

161

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A subset of peripheral blood T lymphocytes coexpressing CD3 and IgG Fc receptors (FcR) (CD16/Leu-11 antigen) have been identified, isolated, and functionally characterized. The CD3+, CD16+ cells were established in short-term culture using growth medium containing interleukin 2 (IL-2). Both the freshly isolated cells and the cultured cell line stably expressed the CD3+, CD16+ phenotype. Furthermore, a majority of these T cells lacked either CD4 or CD8 expression. Like in vitro-activated cytotoxic T lymphocytes and natural killer (NK) cells, the CD3+, CD16+ cells showed numerous azurophilic granules. Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC). The Ig isotype specificity of the ADCC was analyzed using an isotype switch-variant family of a murine anti-HLA monoclonal antibody (mAb). Similar to the CD3-, CD16+ NK cell population, the CD3+, CD16+ T cells preferentially used the IgG2a antibody to mediate ADCC. The CD3+, CD16+ cells demonstrated a proliferative response when cocultured with either a NK-sensitive tumor cell line, K562, or a NK-insensitive B lymphoblastoid cell line, CCRF-SB. The response against CCRF-SB was significantly inhibited by anti-IL-2 receptor antibody, whereas the response against K562 was only partially diminished. Cytotoxicity was also induced in the CD3+, CD16+ population by the presence of anti-CD3 mAb, indicating that cytotoxicity can be triggered by stimulation via the CD3-T cell antigen receptor complex. By isolating these CD3+, CD16+ cells from the peripheral blood of a normal, healthy individual, it has been possible to extensively study the morphology, antigenic phenotype, and functional behavior of this unique subset of T lymphocytes expressing IgG FcR.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).

Lanier¹,

Kipps²,

Phillips³

1985

The Journal of Experimental Medicine

161

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“…Since the first reported patients with a T-CLL-related disease and an unexpectedly indolent clinical course [3,4], similar cases have been recorded with increasing frequency (see re view in [2] and [5]). A careful analysis of the cells expanded in virtually all these patients has shown that these cells express Tsuppressor markers and have morphologic features of granular lymphocytes (GL) [6].…”

Section: The Lymphoproliferative Disease Of Granular Lymphocytes (Ldgl)mentioning

confidence: 72%

“…and CDS). Although the LDGL patients have expanded cells with the morphology of NK cells, the in vitro activity often shows a defect of NK function [2,5], Clinically, although patients with LDGL usually have periph eral blood and bone marrow lymphocytosis, suggesting a di agnosis of CLL, the number of expanded cells is often low (below 10,000 GL/mm\ the common minimal criterion for CLL). We formulate the diagnosis of LDGL after one deter mination of at least 2,000 GL/nr in the peripheral blood.…”

Section: The Lymphoproliferative Disease Of Granular Lymphocytes (Ldgl)mentioning

confidence: 99%

Relevance of Monoclonal Antibody Phenotyping and of Genetic Studies in the Classification of T-Cell Leukemia/Lymphoma

Pandolfi¹,

Cafaro²,

Scarselli³

1987

Oncol Res Treat

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In this short review we discuss two clinical entities characterized by the accumulation in the blood of mature lymphocytes bearing T-cell markers (formerly T-cell chronic lymphocytic leukemia or T-CLL). The lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the expansion of granular lymphocytes (GL). Clinically most patients have a benign clinical course, while some have neutropenia. The neoplastic or reactive nature of the disease is discussed. T-CLL with a T-helper phenotype is, on the other hand, an aggressive disease with poor survival. Patients may be classified into two subgroups according to the presence of serum antibodies against HTLV-I. The possible etiological role of HTLV-I in the disease is discussed.

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“…More complete immunophenotypic features of MNCL cells can be found in several references (Stromberg & Vogtsberger 1983; Reynolds et al. 1984 ; Reynolds 1985 ; Ward et al. 1990 ).…”

Section: Mononuclear Cell Leukemiamentioning

confidence: 95%

The legacy of the F344 rat as a cancer bioassay model (a retrospective summary of three common F344 rat neoplasms)

Maronpot

Nyska

Foreman

et al. 2016

Critical Reviews in Toxicology

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The Fischer 344 (F344) rat was used by the National Toxicology Program (NTP) for over 5 decades for toxicity and carcinogenicity studies. However, in 2006, the NTP decided to switch to a different rat stock due largely to high background control incidences of Leydig cell tumors (LCTs) and mononuclear cell leukemia (MNCL), also known as large granular lymphocytic (LGL) leukemia. In the current review, we aim (1) to provide a summary of NTP bioassays with treatment-associated effects involving MNCL and LCTs in addition to male F344-specific tunica vaginalis mesothelioma (TVM); (2) to describe important pathobiological differences between these F344 rat tumor responses and similar target tissue-tumor response in humans; and (3) to present the NTP reasons for switching away from the F344 rat. We show that due to the highly variable background incidence of F344 MNCL, more reliance on historical control data than is usual for most tumor responses is warranted to evaluate potential effect of any chemical treatment in this rat strain. The high spontaneous incidence of LCTs in the testes of male F344 rats has made this tumor endpoint of little practical use in identifying potential testicular carcinogenic responses. TVM responses in F344 rats have a biological plausible relationship to LCTs unlike TVM in humans. Given their high spontaneous background incidence and species-specific biology, we contend that MNCL and LCT, along with TVM responses, in F344 rat carcinogenicity studies are inappropriate tumor types for human health risk assessment and lack relevance in predicting human carcinogenicity.

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Large granular lymphocyte (LGL) lymphoproliferative diseases: Naturally cytotoxic tumors in man and experimental animals

Cited by 8 publications

References 99 publications

Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).

Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).

Relevance of Monoclonal Antibody Phenotyping and of Genetic Studies in the Classification of T-Cell Leukemia/Lymphoma

The legacy of the F344 rat as a cancer bioassay model (a retrospective summary of three common F344 rat neoplasms)

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