title: Interleukin 2 responsive lymphocytes in patients with adenosine deaminase deficiency.
abstract: We evaluated the effects of recombinant interleukin 2 (IL-2) on the proliferative responses to mitogens of peripheral blood mononuclear cells (PBMC) from three adenosine deaminase (ADA)-deficient patients. There was significant enhancement by IL-2 of the proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) of PBMC from all three patients. We found that normal PBMC respond with increased numbers of CD3-positive cells when exposed to PHA or PWM and that the response by normal CD8-positive cells was greater than that by CD4-positive cells. In contrast, we found that in ADA-deficient cells the response is almost entirely due to the CD3/CD4-positive population of lymphocytes. These results could not be explained by either the culture conditions or the possibility of a mixed chimeric state. When we evaluated an in vitro cell model of ADA deficiency using an ADA inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), we found that the inhibitory effect of EHNA plus deoxyadenosine on mitogen-stimulated PBMC could not be prevented by IL-2. These results suggest that the immunodeficiency in ADA deficiency includes the absence or failure of a subset of T cells to make IL-2 and the failure of the CD8-positive subset to respond to IL-2. Also, the in vitro cell model of ADA deficiency using EHNA as the ADA inhibitor is limited in its use in understanding the pathogenesis of this disease.
authors.affiliation: Department of Pediatrics, University of California, San Francisco 94143.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cowan
authors.forename: W
authors.initials: W
authors.lastname: Smith
authors.forename: A J
authors.initials: AJ
authors.lastname: Ammann
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000172:deficiency*; D058892:Adenosine Deaminase Inhibitors; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology*; D007376:Interleukin-2 / Q000172:deficiency / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D008954:Models, Biological; D009700:Nucleoside Deaminases / Q000172:deficiency*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D007376:Interleukin-2; D008934:Mitogens; D011994:Recombinant Proteins; C010192:9-(2-hydroxy-3-nonyl)adenine; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000225:Adenine