No abstract

Interaction between CD40 on B cells and CD40 ligand molecules on T cells is Two antigen nonspecific ligand receptor systems have been distinguished that mediate efficient activation of T and B cells. The first system is characterized by the interactions of CD28 and CTLA-4 on T cells with their physiological counter receptors, the B7 molecules, expressed on B cells and other antigen presenting cells (reviewed in ref. 1). CD28 is found both on resting and activated T cells, while CTLA-4 is expressed only after successful stimulation of T cells (2). The B7 family of receptors consists at present of two cloned molecules, B7.1 and B7.2, and a putative third member, B7.3 (3). Although crosslinking of CD28 alone does not deliver an activation signal to resting T cells, stimulation of preactivated T cells with anti-CD28 monoclonal antibodies (mAb) results in a vigorous proliferative response and marked secretion of multiple lymphokines (1). Conversely, prevention of signaling through CD28 in a cognate T-B cell interaction using Fab fragments of an anti-CD28 antibody results in abrogation of antigen-specific proliferation and in failure to respond to a subsequent antigenic challenge (4, 5).The second receptor ligand system important for lymphocyte activation involves the binding of the B-cell antigen CD40 to its physiological ligand, CD40 ligand (CD40L) expressed on activated T cells. Ligation of CD40 on B cells mediates a wide range of biological activities including homotypic adhesion, proliferation, expression of costimulatory molecules B7.1 and B7.2, and Ig isotype switching (6-9). CD40L is transiently expressed predominantly on CD4+ T cells after T-cell receptor (TCR) triggering and independently of CD28/CTLA-4 costimulation (7, 10).

Control of growth and differentiation during mammalian embryogenesis is regulated by growth factors from embryonic and/or maternal sources. Cytokines are polypeptide growth factors that are released by a variety of activated immune and nonimmune cells. To identify novel members of the cytokine family that could be involved in the growth and differentiation of the preimplantation embryo, we studied the expression pattern of several genes encoding cytokines and their receptors during mouse preimplantation development in vitro We found that poly(A)+ mRNAs for IL-1, IL-3, IL-6, IL-7, and TNFα are differentially expressed at several stages of mouse preimplantation development, including unfertilized oocytes. Immunostaining of preimplantation embryos using monoclonal antibodies specific for several cytokines and their receptors revealed that at least some of these mRNAs are translated into mature proteins during preimplantation development (IL-1, IL-6, and TNFα). Positive staining for IL-1 and IL-6 receptors was also detected at these stages of development. The controlled expression of these “inflammatory-type” cytokines and their receptors suggests a role for these growth factors during the early phases of mouse ontogeny.