T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1.

Abstract

Studies using monoclonal antibodies (mAbs) have implicated the homodimeric glycoprotein CD28 as an important regulator of human T-cell activation, in part by posttranscriptional control of cytokine mRNA levels. Although the CD28 antigen has functional and structural characteristics of a receptor, a natural ligand for this molecule has not been identified. Here we show that the CD28 antigen, expressed in Chinese hamster ovary (CHO) cells, mediated specific intercellular adhesion with human lymphoblastoid and leukemic B-cell lines and with activated primary murine B cells. CD28-mediated adhesion was not, dependant upon divalent cations. Several mAbs were identified that inhibited CD28-mediated adhesion, including mAb BB-1 against the B-cell activation antigen B7/BB-1 and some mAbs against major histocompatibility complex class I antigens. B7/BB-1 expression correlated closely with CD28-mediated adhesion, but class I expression did not. Transfected COS cells expressing the B7/BB-1 antigen adhered to CD28+ CHO cells; this adhesion was blocked by mAbs to CD28 and B7/BB-1. The specific recognition by CD28 of the B-cell activation antigen B7/BB-1 represents a heterophilic interaction between members of the immunoglobulin superfamily that may serve to regulate T-cell cytokine levels at sites of B-cell activation.The generation of a T-lymphocyte immune response is a complex process involving cell-cell interactions (1) and production of soluble immune mediators (cytokines or lymphokines) (2). This response is regulated by several T-cell surface molecules, including the T-cell receptor complex (3) and other "accessory" surface molecules (1).One such accessory molecule is the CD28 antigen, a homodimeric glycoprotein of the immunoglobulin superfamily (4) found on most mature human T cells (5). Current evidence suggests that this molecule functions in an alternative T-cell activation pathway distinct from that initiated by the T-cell receptor complex (for review, see ref. 6). Monoclonal antibodies (mAbs) to CD28 can augment T-cell responses initiated by various polyclonal stimuli (5-7). These stimulatory effects may result from mAb-induced cytokine production (8) as a consequence of increased mRNA stabilization (9). Anti-CD28 mAbs can also have inhibitory effects; i.e., they can block autologous mixed lymphocyte reactions (10) and activation of antigen-specific T-cell clones (11).The in vivo function of CD28 is not known, although its structure (4) suggests that like other members of the immunoglobulin superfamily (12) it might function as a receptor. CD28 could conceivably function as a cytokine receptor, although this seems unlikely since it shares no homology with other lymphokine or cytokine receptors (4).Alternatively, CD28 might be a receptor that mediates cell-cell contact. In this paper, we describe experiments designed to test this possibility. For this purpose, we have taken an approach based on experiments used to demonstrate intercellular adhesion mediated by major histocompatibility complex (MHC) class I ...

Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression

“…Besides signalling through the T cell receptor/CD3 complex costimulatory molecules play an essential role. Both in vivo and in vitro it has been demonstrated that interaction of CD28 on T cells with its ligand B7 on APC fulfils this role [14]. In the present study, performed in cultures on Ficoll-Hypaque-isolated PBMC, in HIV-1 asymptomatic and in HIV ÿ individuals, T cell responses to CD3 plus CD28 MoAb were considerably enhanced ( 10-fold) compared with T cell responses to CD3 MoAb alone.…”

“…The interaction of the membrane antigen CD28, present on T cells with the counterstructure B7, on antigen-presenting cells (APC) supplies a costimulatory activation signal for T cell proliferation [14]. CD28 is expressed on almost all normal CD4 T cells and on most circulating CD8 T cells [15].…”

The absence of CD56 (NCAM) on malignant plasma cells is a hallmark of plasma cell leukemia and of a special subset of multiple myeloma

“…Indeed, we have found that CD28 was expressed with its ligand CD86 (but not CD80) on myeloma cells, 13 and it has been documented that CD28 mediated adhesion of T cells with B cells by interacting with its ligand. 23 Of note, although we and others were unable to define a function of CD28 on myeloma cells, this molecule is clearly functional. 13,24 Finally, the mechanisms involved in the upregulation of CD28, as those involved in that of CD56, remain unknown.…”

Interferon-alpha gene therapy in combination with CD80 transduction reduces tumorigenicity and growth of established tumor in poorly immunogenic tumor models

“…8 CD80 and CD86 bind to CD28 on T cells, induce serine/threonine phosphorylation of CD28, 9 and transduce signals important for T cell clonal expansion. [10][11][12][13] The CD80/86-CD28 interaction is a necessary and sufficient costimulant for CD8 + CTL generation in the absence of exogenous help, 14 and interaction between antigen-MHC complex and the TCR without costimulation may lead to T cell clonal anergy or apoptosis. 15 Inoculation of tumor cells transduced with CD80 enhances the induction of antitumor immunity.…”