title: Impaired T cell signal transduction through CD28 in a patient with idiopathic thrombocytopenia.
abstract: We describe an infant whose peripheral blood mononuclear cells were unable to proliferate or synthesize IL-2 in response to a mitogenic combination of antibodies directed against CD2 and CD28. This peculiar defect, which has been stable to date, was attributed to an impairment in CD28-mediated T cell activation, because further comitogenic combinations containing anti-CD28 monoclonals also failed to induce normal proliferation of the patient's T cells. In contrast, proliferation after membrane stimulation (with anti-CD2, recombinant IL-2, or certain lectins) or transmembrane activation (with phorbol ester and calcium ionophore) was normal, suggesting that his lymphocytes did not have a general membrane or intracellular signalling impairment. A T cell line derived from the patient confirmed the existence of a severe defect in CD28-mediated T cell proliferation, but also showed a profound impairment in CD3-induced T cell proliferation. Other cell surface molecules like CD2 and CD25 were, in contrast, capable of transducing normal proliferation signals. As all relevant molecules were detectable by cytofluorography and immunoprecipitation, we conclude that the patient's lymphocytes had an intrinsic defect in the delivery of CD28-mediated signals which, in the absence of monocytes, also affected CD3-mediated proliferation. The study of this novel kind of immunodeficiency may help to unravel the complex interactions that take place among CD2, CD3 and CD28 during T cell activation. The presence of an idiopathic thrombocytopenia in the patient suggests the intriguing possibility of a role for CD28 in the maintenance of peripheral blood platelets levels, although alternative interpretations are not ruled out.
authors.affiliation: Department of Immunology, Hopital 12 de Octubre, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pérez-Blas
authors.forename: A
authors.initials: A
authors.lastname: Arnaiz-Villena
authors.forename: R
authors.initials: R
authors.lastname: Góngora
authors.forename: O G
authors.initials: OG
authors.lastname: Segurado
authors.forename: J L
authors.initials: JL
authors.lastname: Vivanco
authors.forename: J R
authors.initials: JR
authors.lastname: Regueiro
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000502:physiology; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013921:Thrombocytopenia / Q000209:etiology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens