Distribution of 5'-nucleotidase in human lymphoid tissues.

Abstract

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)

Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast carcinoma

“…Ecto-5'-NT is a novel maturation marker for both T and B cells since the enzyme activity in peripheral blood T cells is approximately 10-fold higher than in thymocytes (Edwards et al, 1979) and since in adult peripheral B cells it is five-to six-fold higher than in foetal spleen or cord blood B cells (Thompson et al, 1986;Bastian et al, 1984). Ecto-5'-NT is encoded on chromosome 6 (Boyle et al, 1988) and is a cell membrane associated enzyme of 69 kDa.…”

Ecto-5′-Nucleotidase Activity in Human T Cell Subsets. DECREASED NUMBERS OF ECTO-5′-NUCLEOTIDASE POSITIVE CELLS FROM BOTH OKT4+ AND OKT8+ CELLS IN PATIENTS WITH HYPOGAMMAGLOBULINEMIA

“…Ecto-5'-NT deficiency cannot be a consequence of immunoglobulin replacement therapy (as has been suggested for decreased PWM responses in nonimmunodeficient children treated with gammaglobulin [47]), since is was detected in two of our patients before the initiation of treatment. Although ecto-5'-NT activity is a marker for T lymphocyte differentiation (22,23,48), with thymocytes having virtually absent activity, it is unlikely that low numbers of T cells with ecto-5'-NT activity in CAG and CVI patients can be explained merely by a block in T cell maturation. The T cells of none of our patients reacted with the monoclonal antibodies OKT10 or OKT6 (data not shown), both of which recognize thymocyte antigens (34).…”

“…Ecto-5'-NT deficiency in CAG and CVI may be partially explained by an absence of mature B lymphocytes, which normally have threeto fivefold higher ecto-5'-NT activity than total T cell preparations (17,20,22). However, the majority of patients with CAG (17,23) and CVI (24) also have decreased (one-third to one-half of normal) ecto-5'-NT activity in total T cell preparations. We have previously shown (21) that Ty cells (T cells with Fc receptors for IgG) have only one-third the ecto-5'-NT activity of T$ cells (T cells with Fc receptor for IgM); however, little is known regarding ecto-5'-NT activity in T cell subsets defined by the monoclonal antibodies OKT4 (helper/inducer) and OKT8 (cytotoxic/suppressor) (25).…”

Ecto-5'-nucleotidase activities in lymphocytes and B lymphoblastoid cell lines from patients with congenital agammaglobulinemia.

“…It is still unknown why a deficiency of ecto-5'-NT in peripheral lymphocytes is demonstrated in some immunodeficient states including CAG. There remains a possibility that ecto-5'-NT may be related to the function of T cells (Edwards et al 1979;Rowe et al 1980; Thompson et al 1980), having an effect on Ig production. Lower ecto-5'-NT activities shown in rosette forming T cells from CAG patients may suggest such a hypothesis.…”