Association between endogenously activated t cells and immunoglobulin‐secreting b cells in patients with active systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is characterized by increased numbers of circulating B cells activated polyclonally to secrete immunoglobulin. Because T cells secrete, or shed, various factors that are functionally important in regulating immunoglobulin production by B cells, a reverse hemolytic plaque assay was developed to quantitate such activated T cells. In this technique, we used a rabbit antiserum raised to supernatants of concanavalin-A-stimulated human lymphocytes. The relevant antigenic specificity of this antiserum is directed toward the shed surface membrane determinant(s) preferentially expressed on activated T cells. Freshly isolated peripheral blood mononuclear cells from 14 SLE patients contained more than 10 times the number of endogenously activated T cells than cells from normal subjects. Within the SLE group, plaqueforming T cells were particularly increased in patients with active disease. By linear regression analysis, a significant positive correlation was revealed between such activated T cells and immunoglobulin-secreting B cells, also measured by a reverse plaque assay (r = circulate in increased numbers in SLE. Additional investigation will be required to define the molecular nature of the T cell product(s) being measured and to clarify the relationship of these findings to the immunoregulatory abnormalities in this disorder. 0.83). It appears that both activated B cells and T cellsPresent investigations of the immunologic abnormalities in systemic lupus erythematosus (SLE) focus on humoral hyperactivity and T cell hypofunction. The hypergammaglobulinemia, autoantibody formation, and elevated antibody titers to exogenous antigens that characterize this disorder are accompanied by increased numbers of circulating B cells endogenously activated to secrete immunoglobulin (1-5) or specific antibodies (6-8). Most investigators have found T cell function to be impaired with respect to mitogen, antigen, or allogeneic lymphocyte responsiveness (9-12); generation of T suppressor cell activity (13-16); and autologous mixed lymphocyte reactivity (17). In general, both T and B cell abnormalities have been most marked in patients who have active SLE.Available technology has limited the assessment of ongoing T cell activation in SLE; however, increased numbers of small lymphocytes that synthesize DNA have been detected in SLE by autoradiographic techniques (18,19). We have developed a reverse hemolvticL daaue a s p L Ibased _nn--tbe-approach originally used in murine systems by Primi et a1 (20)] that quantitates activated T cells, both in mononuclear cell preparations from freshly isolated peripheral blood and after in vitro culture in the presence of various mitogens and antigens (21). In the present study, this method has been applied to the analysis of circulating T cells in SLE. From the data, it appears

Correction of interleukin-2 production in patients with systemic lupus erythematosus by removal of spontaneously activated suppressor cells.

“…There are other reports of spontaneously activated blood mononuclear cells in SLE. We have described spontaneously proliferating cells (25) and others have reported evidence of activated T cells in this disorder (26). Because removal of suppressor cells from the cell suspensions of some normal donors also elevated IL-2 production, it is likely that the findings in SLE reflect augmentation of a physiologic regulatory mechanism instead of an aberrant phenomenon.…”

Inhibition of soluble antigen-induced T cell proliferation by warm-reactive antibodies to activated T cells in systemic lupus erythematosus.

“…Many immune system functional abnormalities are recognized in systemic lupus erythematosus (SLE),' including defective T cell proliferative response to various specific and nonspecific stimuli (1)(2)(3)(4); impaired natural killer (5,6), antibody-dependent (7,8) and T cell-mediated (9, 10) cytotoxicity; failure of suppression in multiple systems (11)(12)(13)(14)(15); increased numbers of spontaneously activated B (13,(16)(17)(18) and T (19,20) cells; and decreased pokeweed mitogen-driven Ig production (13,18 (21), which carry over to in vitro experiments.…”

Pathogenic T cells in murine lupus exhibit spontaneous signaling activity through phosphatidylinositol 3‐kinase and mitogen‐activated protein kinase pathways

“…T cells play a central role in the pathogenesis of both human and murine lupus (1)(2)(3)(4)(5)(6)(7). For example, pathogenic autoantibodies in lupus are typically IgG, a T cell-dependent isotype, and exhibit features of an antigen-driven response (e.g., somatic mutation and clonal expansion) (8,9).…”