Biomedical subjects

M T Fierro

Publications and source records attributed to M T Fierro.

61 records · Page 4Linked to original sources

PubMed1984

Effects of 12-o-tetradecanoyl-phorbol-13-acetate (TPA) on the colony growth of human T lymphocytes.

The T colony promoting activity of 12-o-tetradecanoyl-phorbol-13-acetate (TPA) was assessed in a double layer culture assay which is dependent on the simultaneous presence of phytohaemagglutinin (PHA) and a leucocyte rich underlayer. TPA (10(-8) M) incorporated in the overlayer in place of PHA was capable of promoting T cell growth in the form of clusters in all 37 experiments performed and in the form of colonies in more than 50% of the samples tested. However, the T colony promoting activity of TPA alone was markedly less evident and consistent than that of PHA (mean 13 +/- 19.9 s.d. colonies vs 168 +/- 78.6). TPA concentrations of 10(-6) M, 10(-9) M and 10(-10) M were practically ineffective. On the other hand, the number of colonies obtained when both TPA 10(8) M and PHA were incorporated in the overlayer was significantly higher (P less than 0.01) than that observed with PHA alone (mean 250 +/- 108.2 vs 178 +/- 84.5 colonies). When TPA concentrations of 10(-9) M and 10(-10) M were used in addition to PHA, the enhancing effect was less evident, while an inhibition of T colony growth was observed with TPA 10(-6) M + PHA. TPA 10(-8) M was also capable of enhancing T colony growth when incorporated in the leucocyte rich underlayer (222 +/- 98.6 vs 172 +/- 80.9 colonies). In all cultures with TPA the peak of growth was delayed compared with that of control experiments with PHA. These findings demonstrate that TPA, particularly when co-cultured with PHA, is an effective T colony promoting agent. The observation that the number of colonies formed in the presence of TPA plus PHA is higher than the sum of those observed with the two stimulators independently, suggests that their synergistic effect may be mediated via the production of colony stimulating soluble factors.

Clone Cells↗

PubMed1983

T-cell functional abnormality in B-chronic lymphocytic leukaemia: evidence of a defect of the T-helper subset.

The helper and suppressor capacity of T, T mu (T non gamma) and T gamma cells was assessed in a group of patients with B-cell chronic lymphocytic leukaemia (B-CLL) in a pokeweed mitogen (PWM) stimulated system. The enriched T-cells (E-rosette positive) from all B-CLL cases showed a reduced capacity to induce the differentiation of normal B-lymphocytes compared with normal T-cells (P less than 0.005). After enrichment of the T mu cells, the helper/inducer capacity was still significantly depressed compared with the same fraction from normal controls (P less than 0.01). On the other hand, enriched T gamma cells from B-CLL were effective in suppressing the differentiation of normal B-lymphocytes to a similar degree as normal T gamma cells. These findings are indicative of a deficient T-cell helper function in B-CLL, which appears to be unrelated to the clinical stage of the disease. The fractionation experiments suggest that this functional impairment is not only due to the abnormal T-cell subset distribution seen in the majority of cases, but point to a possible intrinsic defect within the T mu cell population.

Aged↗

PubMed1983

Normal helper T-cell function in hairy-cell leukaemia.

The function of peripheral blood T-lymphocytes was tested in a series of untreated patients with hairy-cell leukaemia (HCL). The in vitro T-colony forming capacity fell within the normal range in 20 of the 22 cases studied. No difference in colony growth was found between splenectomized and non splenectomized patients. The ability to induce differentiation of normal B-lymphocytes into antibody producing plasma cells, in a pokeweed mitogen (PWM) stimulated system, was similar to that of normal T-cells in all 6 cases studied. Both the T-colony growth and the helper capacity were unrelated to the distribution of T-lymphocyte subsets defined by monoclonal antibodies, despite an increase in OKT8+ cells (suppressor/cytotoxic phenotype) and a decrease in OKT4+ cells (helper/inducer phenotype) in 44% of the patients. The significance of these findings is discussed in relation to T-cell abnormalities previously described in other B-cell leukaemias, chiefly chronic lymphocytic leukaemia (B-CLL). The preserved T-cell function in HCL correlates well with the normal humoral immunity found in this disease.

Antibodies, Monoclonal↗

PubMed1983

Relevance of monoclonal antibodies in the diagnosis of unusual T-cell acute lymphoblastic leukaemia.

3 cases of adult acute lymphoblastic leukaemia (ALL), the T-cell nature of which was identified only using a panel of monoclonal antibodies (MoAb), are described. All cases were E-rosette negative, surface immunoglobulin (SmIg) negative, common ALL (CALLA) antigen negative, terminal deoxynucleotidyl transferase (TdT) positive, and acid phosphatase positive. The T-cell origin of the blasts was demonstrated by the positivity with RFA-1, a MoAb which detects an antigen of MW 65-69000 present on the membrane of thymocytes and mature T-lymphocytes. In addition, 2 of the 3 cases were positive with OKT6, which recognizes cortical thymocytes. MoAb directed against more mature T lineage cells (OKT3, OKT4, OKT8, OKT11A) were consistently negative (less than or equal to 12%). These findings indicate that the use of a combination of MoAb is important in detecting individual cases of T-ALL, which otherwise might be classified as undifferentiated acute leukaemia or null-ALL. MoAb detecting a T-cell antigenic determinant of MW 65-69000 (e.g. RFA-1, OKT1, Leu1) appear the most specific reagents for T-ALL.

Adolescent↗

PubMed1982

[OK T-positivity in stimulated T-lymphocytes].

T-lymphocytes express different antigenic determinants which can be recognized using specific anti-T monoclonal antibodies. OK T3 (Ortho Diagnostics, Raritan, N.J.) detects 95% circulating T-lymphocytes, while OK T4 reacts with helper/inducer T-lymphocytes and OK T8 with suppressor/cytotoxic T-lymphocytes. In normal peripheral blood the proportion of mononuclear cells (after "Lymphoprep' separation) positive with the various anti-T monoclonal antibodies is, according to our standards, as follows: OK T3 77 +/- 9.4%, OK T4 51 +/- 7.8%, OK T8 27+/- 6.4%. In this study we have evaluated the positivity with OK T MoAb after activation and proliferation of the T-cell population in a double layer T-lymphocyte colony assay. After 4-5 days of incubation, the proportion of OK T3 + cells had increased to 94 +/- 4.6%, while that of OK T4+ and OK T8+ had raised to 62 +/- 14.1% and 65 +/- 7.1% respectively. These data suggest that T-colony formation gives rise to an increased expression of OK T8 positivity, possibly through a mechanism of T-cell activation (shown also by the 'Ia' positivity), and/or of proliferation of T-cells with a double antigenic phenotype.

Antibodies, Monoclonal↗

PubMed1982

[Effect of human plasma on the in vitro formation of T-lymphocyte colonies].

T-lymphocyte colonies can be obtained from normal human peripheral blood and bone marrow, using a double layer technique which requires the simultaneous presence of peripheral blood irradiated leucocytes in the underlayer and phytohaemagglutinin in the overlayer (Foa & Catovsky, Clin. Exp. Immunol., 36, 488, 1979). The absence of either of these two factors unables colony formation. In an attempt to improve the plating efficiency 15% autologous plasma was added to the leucocyte rich underlayer, or tested alone. The results demonstrated that both leucocytes and plasma alone show a similar colony promoting activity, giving rise respectively to 160 +/- 80.4 SD and 180 +/- 113.5 SD T-colonies. The combination of both factors produced a significant increase in growth, with an overall mean of 410 +/- 190.5 colonies. Increasing concentration of plasma (1%, 5%, 10%, 15%) gave rise to a dose-dependent increase in colony growth. Furthermore, the simultaneous presence of leucocytes and plasma in the underlayer enabled good colony formation with as little as 0.1 x 105 tes cells in the overlayer. These findings indicate that both human peripheral blood leucocytes and plasma possess T-colony stimulating activity, and that optimal growth is achieved with the combination of these two factors in the underlayer.

Blood Physiological Phenomena↗

PubMed1982

Chronic T-cell leukaemias. III. T-colonies, PHA response and correlation with membrane phenotype.

The functional capacity of T lymphocytes from 28 cases of chronic T-cell leukaemia--T-CLL, T-PLL, T-LCL and Sézary syndrome--was evaluated in a T-colony forming system and in a PHA response assay. Reduced or absent T-colony growth was observed in 23 cases (82%) while in five the growth was normal. Although a good correlation was generally observed between colony formation and PHA transformation, in a few cases a low PHA response was accompanied by moderate colony growth and vice versa. Characterization of the leukaemic T lymphocytes using monoclonal antibodies (OKT series) indicates that cases with a helper/inducer phenotype (OKT4+) showed moderately reduced or near-normal T-colony numbers, whilst cases with a suppressor/cytotoxic phenotype (OKT8+)--confined to T-CLL in this study--had a very low or absent colony growth. The functional abnormalities reported here suggest that neoplastic T-cells with a helper/inducer phenotype show a low proliferative response in the assay systems used, although expressing mature T-cell characteristics. The low growth observed in T-CLL confirms that cells with a suppressor/cytotoxic phenotype form few T-cell colonies.

Cell Division↗