CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes.

Abstract

SurnrrlliryEngagement of the CD3/T cell antigen receptor complex on small, resting T cells is insufficient to trigger cell-mediated cytotoxicity or to induce a proliferative response. In the present study, we have used genetic transfection to demonstrate that interaction of the B7-BB1 B cell activation antigen with the CD28 T cell differentiation antigen costimulates cell-mediated cytotoxicity and proliferation initiated by either anti-CD2 or anti-CD3 monoclonal antibody (mAb). Moreover, a B7-negative Burkitt's lymphoma cell line that fails to stimulate an allogeneic mixed lymphocyte response is rendered a potent stimulator after transfection with B7. The mixed leukocyte reaction proliferative response against the B7 transfectant is inhibited by either anti-CD28 or B7 mAb. We also demonstrate that freshly isolated small, resting human T cells can mediate anti-CD3 or anti-CD2 mAb-redirected cytotoxicity against a murine Fc receptor-bearing mastocytoma transfected with human B7. These preexisting cytotoxic T lymphocytes in peripheral blood are present in both the CD4 and CD8 subsets, but are preferentially within the CD45RO + "memory" population. While small, resting T cells apparently require costimulation by CD28/B7 interactions, this requirement is lost after T cell activation. Anti-CD3 initiates a cytotoxic response mediated by in vitro cultured T cell clones in the absence of B7 ligand. The existence of functional cytolytic T cells in the small, resting T cell population may be advantageous in facilitating rapid responses to immune challenge. CD28 is a disulfide-linked homodimer that is expressed on the majority of human peripheral blood T cells (6, 7). mAbs against CD28 in conjunction with phorbol ester induce T cell proliferation (7) and augment proliferation induced by anti-CD3 or anti-CD2 mAb (8-12). Anti-CD28 mAb-induced proliferation is IL-2 dependent (7, 8) and possibly results from stabilization of messenger RNA for IL-2 and other cytokines (13).Recently, it has been demonstrated that a B cell activation antigen, B7 (14) or BB1 (15), is a natural ligand for CD28 and that this receptor/ligand interaction mediates heterotypic adhesion (16). Interaction of CD28 and B7 results in augmentation of T cell proliferation and cytokine production, and antibodies against CD28 or B7 inhibit alloantigen and mitogen-induced proliferative responses (16,17). B7 is weakly expressed on resting B cells and monocytes, and is elevated after stimulation with pokeweed mitogen, anti-Ig, anti-HLA class II, and EBV (14,15,17). Therefore, it is likely that T cell activation via CD28 will depend on the capacity of the APC to upregulate expression of B7. The importance of the CD28/B7 interaction in polyclonal mitogenic responses prompted us to investigate whether the binding orB7 to CD28

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection

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Functional Consequences of Interactions between Human NKR-P1A and Its Ligand LLT1 Expressed on Activated Dendritic Cells and B Cells

“…To further assess the role of NKR-P1A in T cells vs NK cells, we used mAb-redirected activation with Fc receptor-bearing mouse P815 stimulator cells, a system we have previously used to crosslink and study inhibitory receptors (e.g., inhibitory KIR) on NK cells (1,26) and activating receptors (e.g., CD3) on T cells (19,27). In this assay system, T cells or NK cells are cocultured with the Fc receptor-bearing P815 cell line in the presence or absence of intact IgG Abs against activating or inhibitory receptors on the T cell and NK cells.…”

Expansion of cytotoxic CD8+ CD28− T cells in healthy ageing people, including centenarians

“…5 Interaction between CD28 and its ligands expressed on professional APC results in potent costimulation of T-cell activation and subsequent proliferation. [6][7][8][9] In human adults a subset of circulating T lymphocytes still poorly defined lacks CD28. 10 These cells might be no longer susceptible to clonal expansion or might use a costimulatory pathway other than CD28.…”