T cells play a central role in the initiation and regulation of the immune response to antigen. Both the engagement of the TCR with MHC/Ag and a second signal are needed for the complete activation of the T cell. The CD28/B7 receptor/ligand system is one of the dominant costimulatory pathways. Interruption of this signaling pathway with CD28 antagonists not only results in the suppression of the immune response, but in some cases induces antigen-specific tolerance. However, the CD28/B7 system is increasingly complex due to the identification of multiple receptors and ligands with positive and negative signaling activities. This review summarizes the state of CD28/B7 immunobiology both in vitro and in vivo; summarizes the many experiments that have led to our current understanding of the participants in this complex receptor/ligand system; and illustrates the current models for CD28/B7-mediated T cell and B cell regulation. It is our hope and expectation that this review will provoke additional research that will unravel this important, yet complex, signaling pathway.

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Phytoplasmas ("CandidatusPhytoplasmaThe phylogenetic tree of mollicutes is composed of two major clades that diverged early in evolution (51). One clade contains the orders Acholeplasmatales and Anaeroplasmatales (AAA clade mollicutes), and the other clade contains the orders Mycoplasmatales and Entomoplasmatales (SEM clade mollicutes) (9). Phytoplasmas, formerly known as mycoplasma-like organisms of plants, form a monophyletic group in the order Acholeplasmatales (51) and were recently assigned to a novel genus, "Candidatus Phytoplasma" (41). Approximately 20 phytoplasma phylogenetic groups have been proposed based on 16S rRNA gene sequences, and new branches are continuously being discovered (69,85). Members of the order Acholeplasmatales are distinct from other mollicutes in several ways. For instance, whereas most mollicutes use UGA as a tryptophan codon instead of a stop codon, a feature they share with mitochondria, the acholeplasmas and phytoplasmas retained UGA as a stop codon (80).