title: Abnormalities in CD69 expression, cytosolic pH and Ca2+ during activation of lymphocytes from patients with systemic lupus erythematosus.
abstract: Several immuno-regulatory abnormalities have been described in SLE patients. T cell dysfunction in SLE includes defective in vitro proliferative responses to several stimuli, reduced IL-2 production and a poor helper function. It has been widely proposed that this defective T cell immunoregulatory function has a key role in the hyperactivity of B cells and auto-antibody production in SLE. However, it has not been elucidated whether or not this cell dysfunction is intrinsic to lymphocytes or is due to other factors such as anti-lymphocyte auto-antibodies. In this study we have evaluated some important early cell activation events in T and non-T lymphocytes from patients with systemic lupus erythematosus (SLE). Peripheral blood lymphocytes from SLE patients and controls were isolated. The intracellular pH (pHi), cytosolic calcium (Ca2+i) and CD69 expression were determined by spectrofluorometry and flow cytometry. Modifications of these parameters in response to protein kinase C (PKC) activators, mitogenic lectins and calcium ionophores were also studied. We found a significant reduction in the increase of pHi in response to PKC activators (PMA) in SLE cells. In addition, the induction of CD69 expression by PMA was significantly lower in T cells from SLE patients. By contrast, freshly isolated non-stimulated SLE cells exhibited a significantly higher pHi, as well as an increased baseline expression of the early cell activation antigen CD69. On the other hand, the increase in Ca2+i in response to a Ca2+ ionophore (4Br-A23187) or thapsigargin in Ca(2+)-free solutions, was smaller in SLE lymphocytes. We concluded that T cells from SLE patients exhibit abnormalities in several key early cell activation events (pHi, Ca2+i and CD69 expression). These abnormalities could have an important role in the T cell dysfunction observed in SLE. The presence of T cells with a preactivated phenotype in the peripheral blood of SLE patients, could be a reflection of the ongoing autoimmune phenomena that is occurring in these patients.
authors.affiliation: Department of Immunology, School of Medicine, University of San Luis Potosí, México.
authors.forename: D
authors.initials: D
authors.lastname: Portales-Pérez
authors.forename: R
authors.initials: R
authors.lastname: González-Amaro
authors.forename: C
authors.initials: C
authors.lastname: Abud-Mendoza
authors.forename: S
authors.initials: S
authors.lastname: Sánchez-Armáss
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007376:Interleukin-2 / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D037181:Lectins, C-Type; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000001:Calcimycin; D002118:Calcium; D002273:Carcinogens; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D007476:Ionophores; D037181:Lectins, C-Type; D011493:Protein Kinase C; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate; D019284:Thapsigargin; D000099192:CD69 Antigens