scholarly journals Decreased ecto-5'nucleotidase activity of peripheral blood lymphocytes in human monoclonal gammopathies: correlation with tumor cell kinetics

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 530-534
Author(s):  
M Massaia ◽  
DD Ma ◽  
M Boccadoro ◽  
F Golzio ◽  
P Gavarotti ◽  
...  

Ecto-5′nucleotidase (5′NT) activity of peripheral blood (PB) lymphocytes was determined in 31 patients with serum monoclonal gammopathies (MG). Twenty-one patients had a diagnosis of multiple myeloma (MM), and ten patients had monoclonal gammopathy of undetermined significance (MGUS). The proliferative activity of the bone marrow plasma cells (LI%) was investigated in 28 of these MG patients by means of tritiated thymidine uptake evaluated by simultaneous autoradiography and cytoplasmic immunofluorescence. 5′NT activity was significantly lower in MG patients as compared with normal controls. MM patients had lower 5′NT activity than MGUS patients, but the difference was not significant. By contrast, MM had significantly higher LI% than MGUS patients. There was a linear regression of 5′NT on LI% which was statistically significant: the higher the LI%, the lower the 5′NT. Because the LI% is an accurate prognostic and monitoring factor in MG, this correlation indicates that 5′NT may be of assistance in predicting the clinical progress of MG patients. In seven MGs, the PB T and B lymphocytes were studied separately. The T cell subpopulation was 5′NT deficient compared to the normal controls, shown as a significant linear regression of T cell 5′NT on the LI%. This suggests that in MG there may be an alteration of nonneoplastic T lymphocytes correlated with tumor growth. The OKT8+ lymphocytes were mainly responsible for the 5′NT deficiency of unseparated T lymphocytes.

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 530-534 ◽  
Author(s):  
M Massaia ◽  
DD Ma ◽  
M Boccadoro ◽  
F Golzio ◽  
P Gavarotti ◽  
...  

Abstract Ecto-5′nucleotidase (5′NT) activity of peripheral blood (PB) lymphocytes was determined in 31 patients with serum monoclonal gammopathies (MG). Twenty-one patients had a diagnosis of multiple myeloma (MM), and ten patients had monoclonal gammopathy of undetermined significance (MGUS). The proliferative activity of the bone marrow plasma cells (LI%) was investigated in 28 of these MG patients by means of tritiated thymidine uptake evaluated by simultaneous autoradiography and cytoplasmic immunofluorescence. 5′NT activity was significantly lower in MG patients as compared with normal controls. MM patients had lower 5′NT activity than MGUS patients, but the difference was not significant. By contrast, MM had significantly higher LI% than MGUS patients. There was a linear regression of 5′NT on LI% which was statistically significant: the higher the LI%, the lower the 5′NT. Because the LI% is an accurate prognostic and monitoring factor in MG, this correlation indicates that 5′NT may be of assistance in predicting the clinical progress of MG patients. In seven MGs, the PB T and B lymphocytes were studied separately. The T cell subpopulation was 5′NT deficient compared to the normal controls, shown as a significant linear regression of T cell 5′NT on the LI%. This suggests that in MG there may be an alteration of nonneoplastic T lymphocytes correlated with tumor growth. The OKT8+ lymphocytes were mainly responsible for the 5′NT deficiency of unseparated T lymphocytes.


PEDIATRICS ◽  
1979 ◽  
Vol 64 (4) ◽  
pp. 515-519
Author(s):  
E. Fred Saunders ◽  
Grant Gall ◽  
Melvin H. Freedman

Granulopoiesis was studied in 10 children with Shwachman's syndrome (chronic neutropenia and exocrine pancreatic insufficiency). Marrow proliferative activity assessed by determination of mitotic indices and tritiated thymidine uptake into granulocytic cells was normal. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system demonstrated normal CFU-C numbers in four patients and reduced numbers in five. The granulocyte colonies formed were indistinguishable from normal colonies morphologically. Production of colony-stimulating activity (CSA) from patients' peripheral blood leukocytes appeared normal when tested on control marrow. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow, and co-culture of patients' peripheral blood lymphocytes with control marrow did not inhibit CFU-C growth. We conclude that in Shwachman's syndrome committed granulocytic stem cells are present, and the numbers detected in vitro vary widely as does the clinical neutropenia. The proliferative activity of recognizable granulocytic cells is normal and neither a deficiency of humoral stimulators nor the presence of serum or cellular inhibitors of granulopoiesis can be demonstrated.


2003 ◽  
Vol 12 (3) ◽  
pp. 131-138 ◽  
Author(s):  
Krzysztof Szyllo ◽  
Henryk Tchorzewski ◽  
Malgorzata Banasik ◽  
Ewa Glowacka ◽  
Przemyslaw Lewkowicz ◽  
...  

Background:Endometriosis, uncontrolled proliferation of ectopic and eutopic endometriotic tissues, is common in women at reproductive age, and may affect fertility. The role of macrophages in the pathogenesis is well proved, but engagement of T cells in the pathogenesis of endometriosis is a matter of controversyAims:T-cell involvement in the pathogenesis of endometriosis was the objective of our study performed on women aged 24-46 years with diagnosed endometriosis. All the patients that were studied underwent diagnostic laparoscopy.Methods:We evaluated the distribution of T-lymphocyte subpopulations in peripheral blood (PB), peritoneal fluid (PF) and in endometriotic tissues (ET), as well as cytokines [interleukin (IL)-2, IL-4, IL-10, IL-12, interferon (IFN)-γ] production by peripheral blood lymphocytes. IFN-γ, tumor necrosis factor (TNF)-α, IL-4 and IL-6 were investigated for their intracellular presence. The experiments were carried out before and after 6 months treatment with the GnRH-Analogous Goserelin (Zeneca Pharmaceuticals). The number of performed investigations is presented. Statistical analysis was performed using Statistica/Win 5.0 software and Student't-test, the paired Studentt-test and Fisher's exact test when appropriate.Results:We have compared the lymphocyte subset re-distribution with regard to the American Fertility Society (AFS) stages and scores, but no differences were observed. The significant increase in CD4:CD8 ratio, the decrease in the number of natural killer (NK) cells in PB and the decrease in CD4:CD8 ratio in PF and ET of women with endometriosis was noted. The diminished IFN-γsecretion by phytohemagglutinim (PHA)-stimulated lymphocytesin vitroderived from women with endometriosis and increased IL-4 production may be responsible for defective immunosurveillance against overgrowth of endometriotic tissues. The diminished NK cells number in PB of women with endometriosis argues for such a hypothesis. The increased deposits of proinflammatory IL-6 and TNF-α in the T lymphocytes of women with endometriosis may be related to T-regulatory lymphocyte function and their inability to suppress cell proliferation in endometriosis. GnRH-Analogous Goserelin treatment normalises cytokine production and induces patient recovery.Conclusions:The significant functional and phenotypic differences between the lymphocytes from healthy women and women with endometriosis were noted. The diminished IFN-γproduction in relation to decreased NK cells number and the increased IL-4 production before the treatment and normalisation after the treatment suggest the involvement of the deregulated T-cell system in the growth stimulation and recruitment of endometriotic cells. The increased CD4:CD8 ratio, IL-6, TNF-α deposits and diminished anti-inflammatory IL-10 production by lymphocytes may participate in the pathogenesis of endometriosis, and may secondarily affect the monocyte/macrophage function.


Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 216-225 ◽  
Author(s):  
Anthony D. Cristillo ◽  
Mirtha J. Macri ◽  
Barbara E. Bierer

Abstract The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein–coupled receptors is necessary for primary immune responses and for homing of leukocytes to lymphoid tissues. Here, we have characterized the signaling pathways in primary T lymphocytes that regulate chemokine gene induction using an RNase protection assay. Dependence on stimulation through the coreceptor CD28 and sensitivity to the calcineurin inhibitors cyclosporine and tacrolimus were studied using purified human peripheral blood lymphocytes. Lymphotactin (Ltn), macrophage inflammatory protein (MIP)–1α, and MIP-1β were all rapidly induced and sensitive to cyclosporine treatment. At later time points, the expression of MIP-1α and MIP-1β, but not of Ltn, was restored despite the inhibition of calcineurin activity. By contrast, the induction of interleukin-8 was delayed and was found to be cyclosporine insensitive. Calcineurin activity of IP-10 mRNA induction was contingent on the specific T-cell stimulation conditions, suggesting that IP-10 expression is modulated by calcineurin-dependent and -independent signaling pathways. Differential chemokine expression profiles result from the engagement of T-cell coreceptors and the requirement for, and the dependence on, calcineurin phosphatase activity.


1983 ◽  
Vol 158 (2) ◽  
pp. 571-585 ◽  
Author(s):  
A Moretta ◽  
G Pantaleo ◽  
L Moretta ◽  
M C Mingari ◽  
J C Cerottini

In order to directly assess the distribution of cytolytic T lymphocytes (CTL) and their precursors (CTL-P) in the two major subsets of human T cells, we have used limiting dilution microculture systems to determine their frequencies. The two subsets were defined according to their reactivity (or lack thereof) with B9.4 monoclonal antibody (the specificity of which is similar, if not identical, to that of Leu 2b monoclonal antibody). Both B9+ and B9- cells obtained by sorting peripheral blood resting T cells using the fluorescence-activated cell sorter (FACS) were assayed for total CTL-P frequencies in a microculture system that allows clonal growth of every T cell. As assessed by a lectin-dependent assay, approximately 30% of peripheral blood T cells were CTP-P. In the B9+ subset (which represents 20-30% of all T cells), the CTL-P frequency was close to 100%, whereas the B9- subset had a 25-fold lower CTL-P frequency. It is thus evident that 90% and 10% of the total CTL-P in peripheral blood are confined to the B9+ or B9- T cell subsets, respectively. Analysis of the subset distribution of CTL-P directed against a given set of alloantigens confirmed these findings. CTL-P frequencies were also determined in B9+ and B9- subsets derived from T cells that had been activated in allogenic mixed leucocyte cultures (MLC). Approximately 10% of MLC T cells were CTL-P. This frequency was increased 3.5-fold in the B9+ subset, whereas the B9- subset contained only a small, although detectable number of CTL-P. Moreover, the great majority of the (operationally defined) CTL-P in MLC T cell population were found to be directed against the stimulating alloantigens, thus indicating a dramatic increase in specific CTL-P frequencies following in vitro stimulation in bulk cultures.


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