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Abnormalities in CD69 expression, cytosolic pH and Ca2+ during activation of lymphocytes from patients with systemic lupus erythematosus

Department of Immunology, Department of Physiology, School of Medicine, University of San Luis Potosi

R. González-Amaro

Department of Immunology, Department of Physiology, School of Medicine, University of San Luis Potosi

C. Abud-Mendoza

Hospital Central 'Dr Ignacio Morones Prieto', San Luis Potosi, S.L.P., México

S. Sánchez-Armáss

Laboratory of Neuronal Physiology, Department of Physiology, School of Medicine, University of San Luis Potosi

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 (pH _i), 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 pH_i 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 pH_i, 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 Ca ²⁺ ionophore (4Br-A23187) or thapsigargin in Ca²⁺-free solutions, was smaller in SLE lymphocytes. We concluded that T cells from SLE patients exhibit abnormalities in several key early cell activation events (pH _i, 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.

Key Words: pHi • systemic lupus erythematosus • cell activation • Ca2+i • CD69

Lupus, Vol. 6, No. 1, 48-56 (1997)
DOI: 10.1177/096120339700600107


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