title: A combined immunodeficiency with oligoclonal CD8+, V beta 3-expressing, cytotoxic T lymphocytes in the peripheral blood.
abstract: The diagnosis severe combined immunodeficiency was made in a male infant at the age of 18 wk. Known causes of severe combined immunodeficiency were excluded. The activity of total 5'-nucleotidase (E.C. 3.1.3.5) in the PBMC was found to be strongly decreased. Analysis of the peripheral blood revealed a lymphocytosis, mainly of CD8+ T cells. These lymphocytes expressed high levels of CD29, CD38, CD45RA, and MHC class II molecules but no CD25, CD26, CD27, or CD28 Ag. The cells proliferated poorly to all T cell stimulants tested and no helper activity for IgM secretion could be induced. In contrast to the poor proliferative responses, high levels of TCR-induced cytolytic activity, without lymphokine-activated killer-cell outgrowth, were induced by CD3 mAb. Analysis of TCR-beta gene rearrangements indicated that two clonal populations constituted the majority of the E-rosette+ peripheral blood fraction. Moreover, the vast majority of the CD8+ cells were found to react with a mAb to V beta 3. Polymerase chain reaction on cDNA from peripheral blood cells with primers that amplify TCR V beta elements showed, in agreement with the fluorescence data, an overrepresentation of V beta 3 but absence of usage of approximately 50% of the other V beta elements. Thus, in a severe combined immunodeficiency patient, CD8+ T cells with limited T cell receptor usage and restricted effector functions were found. The observed alterations in the 5'-nucleotidase levels may be secondary to the outgrowth of this population.
authors.affiliation: Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.
authors.forename: K C
authors.initials: KC
authors.lastname: Kuijpers
authors.forename: J J
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: P
authors.initials: P
authors.lastname: van der Burg
authors.forename: M T
authors.initials: MT
authors.lastname: Roos
authors.forename: J
authors.initials: J
authors.lastname: Vonk
authors.forename: R
authors.initials: R
authors.lastname: de Abreu
authors.forename: D
authors.initials: D
authors.lastname: de Korte
authors.forename: C J
authors.initials: CJ
authors.lastname: van Noesel
authors.forename: R S
authors.initials: RS
authors.lastname: Weening
authors.forename: R A
authors.initials: RA
authors.lastname: van Lier
mesh_terms: D015720:5'-Nucleotidase / Q000032:analysis; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001483:Base Sequence; D016827:CD8 Antigens / Q000032:analysis*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016827:CD8 Antigens; D007136:Immunoglobulins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015720:5'-Nucleotidase