A new method for the detection of Lesch-Nyhan heterozygotes by peripheral blood T cell culture using T cell growth factor

Abstract Thioguanine-resistant T lymphoblast populations were selectively amplified using T cell growth factor in the cultures of peripheral blood T cells from four Lesch-Nyhan heterozygotes. Although Lesch-Nyhan T lymphoblasts were all thioguanine-resistant, none of the cultures from 13 control subjects yielded the growth of such defective cell populations. These data provide direct evidence for the existence of a small percentage (5%–40%) of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficient T cells in the heterozygotes, but not in normal individuals. Conversely, culture of the T lymphoblasts with azaserine plus hypoxanthine permitted the growth of the other part of the cell population that was enzyme positive. The low percentages of HGPRT-negative cells among T cells in heterozygotes suggest that the presence of this enzyme is beneficial for differentiation of lymphocytes of T cell linkage. Considering the ease and the reliability, culture of the peripheral T cells with thioguanine and T cell growth factor is very likely of practical use for detecting Lesch-Nyhan syndrome carriers among predisposed females.

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A new method for the detection of Lesch-Nyhan heterozygotes by peripheral blood T cell culture using T cell growth factor

Blood ◽

10.1182/blood.v63.4.912.bloodjournal634912 ◽

1984 ◽

Vol 63 (4) ◽

pp. 912-916

Author(s):

N Kamatani ◽

H Yamanaka ◽

K Nishioka ◽

T Nakamura ◽

K Nakano ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Growth Factor ◽

Cell Growth ◽

Peripheral Blood ◽

Normal Individuals ◽

T Cell Growth ◽

Hypoxanthine Guanine Phosphoribosyltransferase ◽

T Lymphoblasts ◽

T Cell Growth Factor

Thioguanine-resistant T lymphoblast populations were selectively amplified using T cell growth factor in the cultures of peripheral blood T cells from four Lesch-Nyhan heterozygotes. Although Lesch-Nyhan T lymphoblasts were all thioguanine-resistant, none of the cultures from 13 control subjects yielded the growth of such defective cell populations. These data provide direct evidence for the existence of a small percentage (5%–40%) of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficient T cells in the heterozygotes, but not in normal individuals. Conversely, culture of the T lymphoblasts with azaserine plus hypoxanthine permitted the growth of the other part of the cell population that was enzyme positive. The low percentages of HGPRT-negative cells among T cells in heterozygotes suggest that the presence of this enzyme is beneficial for differentiation of lymphocytes of T cell linkage. Considering the ease and the reliability, culture of the peripheral T cells with thioguanine and T cell growth factor is very likely of practical use for detecting Lesch-Nyhan syndrome carriers among predisposed females.

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Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells

Blood ◽

10.1182/blood.v59.6.1330.1330 ◽

1982 ◽

Vol 59 (6) ◽

pp. 1330-1336 ◽

Cited By ~ 16

Author(s):

C Tarella ◽

FW Ruscetti ◽

BJ Poiesz ◽

A Woods ◽

RC Gallo

Keyword(s):

T Cells ◽

T Cell ◽

Growth Factor ◽

Cell Growth ◽

T Lymphocytes ◽

Cell Lines ◽

Humoral Factors ◽

Human T Cells ◽

T Cell Growth ◽

T Cell Growth Factor

Abstract Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.

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Human P40 T-cell growth factor (interleukin-9) supports erythroid colony formation

Blood ◽

10.1182/blood.v75.12.2271.2271 ◽

1990 ◽

Vol 75 (12) ◽

pp. 2271-2275 ◽

Cited By ~ 81

Author(s):

RE Donahue ◽

YC Yang ◽

SC Clark

Keyword(s):

Bone Marrow ◽

T Cell ◽

Growth Factor ◽

Cell Growth ◽

Cell Line ◽

Peripheral Blood ◽

Colony Formation ◽

T Cell Growth ◽

Interleukin 9 ◽

T Cell Growth Factor

Abstract Because human P40 T-cell growth factor, tentatively designated interleukin-9 (IL-9), was isolated through its ability to stimulate a human IL-3-dependent leukemic cell line (M-O7E), we tested the ability of IL-9 to support the growth and differentiation of normal hematopoietic progenitor cells from peripheral blood and bone marrow. Although the M-O7E cell line was derived from a patient with megakaryoblastic leukemia, IL-9 has not proved to be a growth or maturation factor for megakaryocytes, but instead has proved to be effective in supporting the development of erythroid bursts (BFU-E) in cultures supplemented with erythropoietin. Using highly purified progenitors from peripheral blood, IL-3 showed a BFU-E plating efficiency of 46% compared with 20% for IL-9. Because of the purity of these cell preparations and the low cell density in culture, IL-9 is likely to interact directly with erythroid progenitors. Analysis of mixing experiments and of the morphology of the BFU-E in culture indicated that IL-9 interacts preferentially with a relatively early population of IL-3-responsive BFU-E. In cultures of human bone marrow or cord blood, IL-9 selectively supported erythroid colony formation, while IL-3 and granulocyte/macrophage colony-stimulating factor additionally yielded granulocyte/macrophage colonies. Therefore, IL-9 represents a new T cell-derived cytokine with the potential for selectively stimulating erythroid development in the hematopoietic system.

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