Induction and separation of antigen-dependent T helper and T suppressor cells in man

Shore, A; Dosch, Hans‐Michael; Gelfand, Erwin W.

doi:10.1038/274586a0

Cited by 122 publications

(52 citation statements)

References 4 publications

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“…Heparinized blood was obtained from healthy individuals, tonsil tissue from otherwise healthy children undergoing tonsillectomy, and thymus tissue from children at the time of cardiac surgery. Mononuclear cells were obtained following Ficoll-Hypaque gradient centrifugation (13). The isolated mononuclear cells were suspended in RPMI 1640 supplemented with 10% fetal calf serum at a concentration of 107 cells/ml.…”

Section: Methodsmentioning

confidence: 99%

Volume regulation by human lymphocytes. Identification of differences between the two major lymphocyte subpopulations.

Cheung¹,

Grinstein²,

Gelfand³

1982

J. Clin. Invest.

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Section: Methodsmentioning

confidence: 99%

Volume regulation by human lymphocytes. Identification of differences between the two major lymphocyte subpopulations.

Cheung¹,

Grinstein²,

Gelfand³

1982

J. Clin. Invest.

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“…T lymphoblasts are killed by deoxyadenosine or deoxyguanosine, rapidly accumulate dATP or dGTP, and have very low levels of 5'-nucleotidase (5-9). In contrast, B lymphoblasts grow normally in deoxyadenosine or deoxyguanosine, accumulate only small quantities of deoxynucleoside triphosphates, and have higher 5'-nucleotidase levels than T lymphoblasts (5-9 and four T lymphoblast lines (CEM, Jurkat, MSB-2, and MOLT-3) were maintained and characterized as described (10).Peripheral lymphocytes were obtained, separated into Erosette forming cells and non-E-rosette forming cells, and characterized by described methods (11)(12)(13). Lymphoid organs were obtained from children with no known immune dysfunction, and cells were separated from these tissues within 1 hr of surgery by using described methods (14) …”

mentioning

confidence: 99%

“…Peripheral lymphocytes were obtained, separated into Erosette forming cells and non-E-rosette forming cells, and characterized by described methods (11)(12)(13). Lymphoid organs were obtained from children with no known immune dysfunction, and cells were separated from these tissues within 1 hr of surgery by using described methods (14) …”

mentioning

confidence: 99%

Distribution of 5'-nucleotidase in human lymphoid tissues.

Edwards¹,

Gelfand²,

Burk³

et al. 1979

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

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Low activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) in T lymphoblasts may explain the marked sensitivity of this cell to deoxynucleotide accumulation when compared to B Iymphoblasts. The relevance of such observations with cultured cells to the normal immune system requires the demonstration of similar differences in the 5'-nucleotidase activity of normal human lymphocyte subpopulations. Sheep erythrocyte (E) rosette-forming cells from normal thymus, tonsi , and peripheral mononuclear cells have 5'-nucleotidase activities of 1.7, 11.3, and 21.2 nmol/hr per 106 cells. Non-E-rosette forming cells from the peripheral blood or tonsil have 5'-nucleotidase activity comparable to the higher levels found in the peripheral E-RFC. Increased levels of5'-nucleotidase activity may be a marker for post-thymic T Iymphocytes.T lymphoblasts have 5'-nucleotidase activity similar to values demonstrated for E-RFC in thymus, whereas cultured B lymphoblasts have 5'-nucleotidase activity 15 times greater than that of T lymphoblasts. On the basis of these observations, the 5'-nucleotidase deficiency in congenital agammaglobulinemia has been reevaluated. In these patients the data indicate that peripheral E-rosette forming cells have the enzyme deficiency, demonstrating an abnormality of T lymphocytes in this disorder of immunoglobulin production. Lymphocyte 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) may have an important role in the regulation of the human immune system. Decreased activity of this purine catabolic enzyme has been observed in patients with primary immunoglobulin deficiency (1-4). However, it remains unclear whether an etiological relationship exists between the immune dysfunction and this enzyme deficiency.A marked difference in 5'-nucleotidase activity has been proposed as the molecular basis for the differential susceptibility of B and T lymphoblast lines to the toxicity related to deoxynucleoside accumulation (5-7). T lymphoblasts are killed by deoxyadenosine or deoxyguanosine, rapidly accumulate dATP or dGTP, and have very low levels of 5'-nucleotidase (5-9). In contrast, B lymphoblasts grow normally in deoxyadenosine or deoxyguanosine, accumulate only small quantities of deoxynucleoside triphosphates, and have higher 5'-nucleotidase levels than T lymphoblasts (5-9 and four T lymphoblast lines (CEM, Jurkat, MSB-2, and MOLT-3) were maintained and characterized as described (10).Peripheral lymphocytes were obtained, separated into Erosette forming cells and non-E-rosette forming cells, and characterized by described methods (11)(12)(13). Lymphoid organs were obtained from children with no known immune dysfunction, and cells were separated from these tissues within 1 hr of surgery by using described methods (14)

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“…Peripheral blood was obtained from healthy adult volunteers and mononuclear cell suspensions (PBM) were prepared by density gradient centrifugation using Ficoll-Hypaque (17). PBM were further divided into Erosetting (E+) and non-E-rosetting (E-) populations by rosette depletion using neuraminidase-treated sheep erythrocytes (18). PBM-E+ populations contained <2.0% monocytes as assessed by nonspecific esterase staining (19) and >95% E-rosetting cells.…”

Section: Methodsmentioning

confidence: 99%

Monocytes are required to trigger Ca2+ uptake in the proliferative response of human t lymphocytes to staphylococcus aureus protein A.

Lederman

Lee

Cheung

et al. 1984

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

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We have used the T-cell mitogen Staphylococcus aureus protein A (SpA) to study the role of monocytes in the early events of T-lymphocyte activation. The mitogenic response of human peripheral blood mononuclear cells (PBM) was compared to the response of populations enriched for T cells by E-rosetting (PBM-E+). In response to SpA, the [3H]thymidine uptake of PBM-E' was reduced by 80% compared to PBM. The reduced response of PBM-E' was completely restored by the addition of irradiated PBM-E-or the monocyte-like human cell line U-937 but not by addition of irradiated PBM-E'. A direct interaction of SpA with monocytes is important since proliferative responses could be generated by preincubation of U-937 with SpA followed by washing and subsequent addition to PBM-E+; incubation of PBM-E+ with SpA followed by washing and subsequent addition of U-937 did not result in a proliferative response. To further delineate the role of the monocyte, we examined the ability of soluble SpA, U-937, or U-937 preincubated with SpA to trigger Ca2+ flux into T lymphocytes, an early step in initiation of the proliferative response. SpA-pretreated U-937, but neither SpA nor monocytes alone, triggered Ca2+ movement into the T lymphocytes. This defines a new role for the monocyte in the early events of T-lymphocyte activation.The monocyte/macrophage is thought to have an important accessory role in T-lymphocyte proliferative responses to antigens and mitogens (1)(2)(3)(4)(5), but the precise mechanisms of monocyte action and their relationship to other early steps in lymphocyte activation are unclear. Proposed monocyte functions include (i) presentation of antigen or mitogen (6), (it) antigen processing (7,8), and (iii) secretion of lymphostimulatory molecules (e.g., interleukin 1) perhaps in concert with antigen presentation (9, 10). It has been difficult to separate clearly these functional properties by using in vitro systems, which usually measure lymphocyte proliferation occumng 72 hr after the initial activating event.Further delineation of the role of monocytes in lymphocyte activation requires identification and measurement of events occurring in the lymphocyte within minutes after activation. Studies of lectin-stimulated mitogenesis have identified such an event: lectin binding triggers a rapid influx of Ca2+ (11)(12)(13)(14)(15), which leads to the formation of an intracellular Ca2+-calmodulin complex (16). The changes in intracellular Ca2' appear to be obligatory early steps in the metabolic cascade leading eventually to DNA synthesis and cell division.In the present study, we have used a monocyte-dependent T-cell mitogen, Staphylococcus aureus protein A (SpA), to examine the participation of monocytes in the induction of Ca2+ movement across T-lymphocyte membranes. Monocytes preincubated with SpA trigger a rapid influx of Ca2+ into lymphocytes, whereas neither SpA nor monocytes alone trigger Ca2+ movement. These studies define a new role for the monocyte in the early events of T-lymphocyte activation. MATERIALS AND ...

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Induction and separation of antigen-dependent T helper and T suppressor cells in man

Cited by 122 publications

References 4 publications

Volume regulation by human lymphocytes. Identification of differences between the two major lymphocyte subpopulations.

Volume regulation by human lymphocytes. Identification of differences between the two major lymphocyte subpopulations.

Distribution of 5'-nucleotidase in human lymphoid tissues.

Monocytes are required to trigger Ca2+ uptake in the proliferative response of human t lymphocytes to staphylococcus aureus protein A.

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