Expression and function of CD28 on Epstein-Barr virus-positive B cell lines and AIDS-associated non-Hodgkin's...

CD28, which is expressed on most T cells, can provide a costimulatory signal during T cell activation. Although principally considered to be a T cell-associated molecule, CD28 has been seen to be expressed on mast cells and natural killer cells, as well as on plasma and myeloma cells, but not on cells representing earlier stages of B cell development. Here were report that CD28 was expressed on Epstein-Barr virus (EBV)-positive B lymphoblastoid and AIDS-associated non-Hodgkin's lymphoma cell lines. These cells also expressed the ligands for CD28, B7-1 and B7-2, but not CTLA-4. Furthermore, peripheral blood B cells infected with EBV ex vivo expressed CD28 after infection. Cross-linking with a stimulatory anti-CD28 antibody resulted in an increased expression of CD71 (transferrin receptor) or CD25 (interleukin-2 alpha receptor subunit). The addition of a blocking CTLA-4-Ig fusion protein, or antisense oligonucleotides for CD28, resulted in a decreased expression of these molecules. In 1 cell line, the addition of an anti-CD28 stimulatory antibody reduced Fas-induced apoptosis, and antisense oligonucleotide-induced inhibition of CD28 expression enhanced Fas-mediated apoptosis. Overall, these results suggest a role for CD28 and its ligands, B7-1 and B7-2, in homotypic interactions in EBV+ B cell lines, which may mediate cellular activation and/or viability.