Abnormalities in CD69 Expression, Cytosolic pH and Ca2+ During Activation of Lymphocytes from Patients with Systemic Lupus Erythematosus  

Oleh:

Pérez, D. Portales ; Amaro, R. González ; Mendoza, C. Abud ; Armáss, S. Sánchez

Jenis: Article from Journal
Dalam koleksi: Lupus vol. 6 no. 1 (1997), page 48-56.
Topik: pH Systemic Lupus Erythematosus; Cell Activation; Ci2; a+ CD69
Fulltext: 48.pdf (767.65KB)

Isi artikel

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 (i)p,H cytosolic calcium (2i)C+a 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 pi H 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 pi,H as well as an increased baseline expression of the early cell activation antigen CD69. On the other hand, the increase in Ci2 a+ in response to a C 2a+ ionophore (4Br-A23187) or thapsigargin in C-2fra+ee solutions, was smaller in SLE lymphocytes. We concluded that T cells from SLE patients exhibit abnormalities in several key early cell activation events (i,pH Ci2 a+ 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.

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