Acquisition of New Migratory Properties by Highly Differentiated CD4+CD28null T Lymphocytes in Rheumatoid Arthritis Disease

Abstract

Expanded CD4+CD28null T lymphocytes are found in the tissues and peripheral blood of patients with many autoimmune diseases, such as rheumatoid arthritis (RA). These highly differentiated cells present potent inflammatory activity and capability to induce tissue destruction, which has been suggested to predispose to the development of more aggressive disease. In fact, preferential migration to inflammatory sites has been proposed to be a contributing factor in the progression of autoimmune and cardiovascular diseases frequently found in these patients. The functional activity of CD4+CD28null T lymphocytes is largely dependent on interleukin 15 (IL-15), and this cytokine may also act as a selective attractor of these cells to local inflammatory infiltrates in damaged tissues. We have analysed, in RA patients, the migratory properties and transcriptional motility profile of CD4+CD28null T lymphocytes compared to their counterparts CD28+ T lymphocytes and the enhancing role of IL-15. Identification of the pathways involved in this process will allow us to design strategies directed to block effector functions that CD4+CD28null T lymphocytes have in the target tissue, which may represent therapeutic approaches in this immune disorder.

Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities

“…Although these senescence processes were described in aging, promoted by the many contacts of the immune system with different antigens throughout life, there were also found in other situations as some chronic diseases [ 51 , 52 ]. Underlying disease, ICU conditions and invasive treatments that are usually applied in critically ill patients, are known to alter the immune system homeostasis producing an immunosenescence phenotype [ 53 , 54 ].…”

Personalized Medicine in Autoimmune Diseases

“…Finally, Rioseras et al analyzed the adhesion and migration abilities of CD4+CD28null T lymphocytes in RA patients, as well as the effect that IL-15 could have in these processes [10]. CD4+CD28null T lymphocytes, increased in RA patients, showed enhanced migration capacity in comparison with their counterparts CD28+ T lymphocytes.…”