Decreased adenosine deaminase (ADA) and 5′nucleotidase (5NT) activity in peripheral blood T cells in hodgkin disease

Abstract

The purine metabolic enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) play an important role in normal lymphocyte differentiation. Abnormal levels of one or all of these enzymes have been associated with immunodeficiency diseases and lymphoproliferative disorders. ADA, PNP, and 5NT activity was measured in peripheral blood T cells from 24 patients with Hodgkin disease (HD) (12 in complete remission and 12 with active disease) to determine whether an association existed between enzyme abnormalities and the decreased cellular immune function previously described in this disorder. HD patients had a significantly decreased absolute lymphocyte count (1,618 +/- 1107/mm3; mean +/- SD) compared to controls (2,320 +/- 980; p less than .001). ADA, PNP, and NT activity was assessed in lymphocyte extracts by measuring the conversion of radiolabeled substrates to products over time. ADA activity expressed as mean +/- SEM nanomoles/10(6) lymphocytes/hr was significantly decreased in T cells from HD patients (84.6 +/- 7.5) compared to controls (128 +/- 12.3; p less than 0.025). Likewise, 5NT was significantly decreased in HD patients (12.7 +/- 1.3) compared to controls (24.0 +/- 3.6; p less than .005). There was not a significant difference in PNP activity between both groups. Low 5NT activity was present irrespective of whether patients had active disease (12.1 +/- 1.5) or were in unmaintained complete remission (14.5 +/- 2.4). These findings suggest that biochemical abnormalities may be responsible for or related to the persistent abnormalities in T-cell function noted throughout the clinical course of HD.

Surface expression of adenosine deaminase in mitogen-stimulated lymphocytes

“…Although this enzyme is present in all mammalian tissues, it appears to have a major role in the development and function of lymphoid tissue. Thus, alterations in the level of the enzyme have been described in several diseases such as acute leukaemia [1], lymphomas [2,3], myasthenia gravis [4] and AIDS [5]. Indeed, some derivatives of adenosine, such as 2'-fluoro-2',3'-dideoxyarabinofuranosyladenine or 2',3'-dideoxyadenosine, are used in the treatment of AIDS [6,7].…”

Cancer Immunotherapy and the Immune Response in Hodgkin Lymphoma

“…The reduced IL-2 levels could not be explained by reduced IL-2 receptor expression in T cells from cHL patients. The observation of a decreased activity of the enzymes adenosine deaminase and 5′ nucleotidase in Hodgkin T cells, both essential for adequate T-cell proliferation, supported the hypothesis that cHL patients have an intrinsic defect for enzymes with relevance for T-cell function ( 18 , 19 ). The same enzyme defect was found in other Epstein–Barr virus (EBV)-positive tumors, and it was speculated that the EBV infection was the common causative link for the observed immunodeficiency.…”

Adenosine inhibits activation‐induced T cell expression of CD2 and CD28 co‐stimulatory molecules: Role of interleukin‐2 and cyclic AMP signaling pathways

“…One question that arises is the degree to which tumor‐infiltrating T cells might be resistant to the immunosuppressive effect of tumor‐associated adenosine as a result of T‐cell‐surface expression of adenosine deaminase in association with CD26 [Dong et al, 1996]. However, adenosine deaminase activity is reported to be significantly lower in the peripheral blood T lymphocytes of cancer patients [Dasmahapatra et al, 1986; Murray et al, 1986], implying increased susceptibility of T cells to adenosine‐mediated inhibition within the tumor microenvironment. Moreover, cytotoxic T lymphocytes possess very low levels of adenosine deaminase activity in comparison to thymocytes and bulk T cell cultures [Minkowski et al, 1984; Minkowski and Bandeira, 1985].…”