Primary T lymphocyte immunodeficiency associated with a selective impairment of CD2, CD3, CD43 (but not CD28)-mediated signal transduction.
A 2-year-old female with important signs of immune response failure against virus, bacteria, fungi and protozoa and no obvious humoral or lymphocyte phenotypical defect was studied. Both peripheral blood mononuclear cells and IL-2-dependent T cell lines derived from the patient showed a severe selective T cell activation impairment via CD2, CD3 and CD43; however, this defect was reversible with the addition of either IL-2, or phorbol myristate acetate (PMA) or anti-CD28 antibodies. Concordantly, the induction of IL-2 (and, in part, IL-3 and IL-4) messenger RNA was severely reduced in stimulated T cells, but that of other cytokines was either normal (IL-5) or only slightly diminished (interferon-gamma (IFN-gamma)). It is concluded that an activation T cell defect exists previous to protein kinase C (PKC) and between membrane receptors and the activation pathway of certain response genes encoding for interleukins involved in proliferation (i.e. IL-2, IL-3 and IL-4), but not of others (i.e. IL-5). The use of T cell lines from human T lymphocyte activation deficiencies allows dissection of T cell pathology and the corresponding physiological pathways. In the present description, there is an evident independence of the CD28 T cell activation pathway from those induced through CD2 or CD3, and the differential gene regulation of the different interleukins.
Rodríguez-Gallego
C
C
Department of Immunology, Universidad Complutense, Hospital 12 de Octubre, Madrid, Spain.
Arnaiz-Villena
A
A
Corell
A
A
Manzanares
J
J
Timón
M
M
Pacheco
A
A
Regueiro
J R
JR
D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018801:CD2 Antigens; D018106:CD28 Antigens / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007239:Infections / Q000276:immunology; D007376:Interleukin-2 / Q000172:deficiency; D051917:Leukosialin; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D012795:Sialoglycoproteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D051917:Leukosialin; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; C465014:SPN protein, human; D012795:Sialoglycoproteins