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Rheumatoid arthritis is a chronic inflammatory polyarthritis whose etiology remains uncertain. Recently we have learned that autoimmunity to citrullinated protein antigens has specificity for rheumatoid arthritis and defines a clinically and genetically distinct form of the disease. Multiple genes contribute to disease susceptibility, with the HLA locus(More)
We conducted a study to determine the prevalence of extraarticular manifestations (ExRA) in a cohort of predominantly Hispanic and Asian patients with rheumatoid arthritis (RA), to identify factors associated with the development of ExRA, and to compare the prevalence of ExRA between Hispanic and Asian patients. Patients with RA followed in the outpatient(More)
CD28 costimulation is essential for CD4(+) T cell proliferation, survival, interleukin 2 (IL-2) production and T helper type 2 development. To define the nature of the signals that may drive different T cell responses, we have done a structure-function analysis of the CD28 cytoplasmic tail in primary T cells. CD28-mediated T cell proliferation and IL-2(More)
Similarities between the inflammatory pathways in atherosclerosis and rheumatoid arthritis (RA) are striking. Chronic systemic inflammation in RA patients leads to cardiovascular (CV) events beyond traditional cardiac risk factors. Clinicians typically focus on treating the joint manifestations of RA while neglecting to eliminate systemic inflammation,(More)
The CD28 homodimer is thought to function as a signal transducing receptor during activation of T cells. Evidence is presented that the degree of aggregation of CD28 on the cell surface regulates two distinct CD28-associated signals. Binding of bivalent CD28 monoclonal antibody (MoAb) 9.3 upregulates lymphokine production by messenger RNA (mRNA)(More)
Antibodies against the T3-antigen receptor complex can activate the human T cell line, Jurkat, to produce interleukin 2 (2-5). This activation is initiated by a receptor-mediated increase in the concentration of free cytoplasmic calcium ions [Ca2+]i (3, 4). In this communication, we investigate the mechanism by which the receptor complex increases [Ca2+ )i(More)
Phorbol esters, such as phorbol myristate acetate (PMA), are known to be potent co-stimulants with calcium ionophores for activation of T lymphocytes. The most extensively studied intracellular effect of PMA is its ability to activate the cytoplasmic enzyme protein kinase C (pkC). Herein, we examined the role of pkC activation during T cell activation.(More)
The MRC OX-44 molecule, which is expressed on all peripheral leukocytes, identifies the subset of thymocytes capable of proliferating in response to alloantigens and lectins (Paterson, D.J., J.R. Green, W.A. Jefferies, M. Puklavec, and A.F. Williams. 1987. J. Exp. Med. 165:1). When we isolated monoclonal antibodies (mAbs) on the basis of their ability to(More)
The cell surface molecule CD2 has a signaling role in the activation of T lymphocytes and natural killer cells. Because perturbation of CD2 leads to the appearance of tyrosine-phosphorylated proteins, we investigated the possibility that CD2 associates with cytoplasmic protein tyrosine kinases. As determined by in vitro kinase assays and phosphoamino acid(More)