Chemokines and T Lymphocytes: More than an Attraction

• Published in: Immunity 1998-07, Vol.9 (1), p.1-11
• Main Authors: Ward, Stephen G, Bacon, Kevin, Westwick, John
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Biomarkers; CD28 Antigens - metabolism; Chemokine CCL5 - metabolism; Chemokines - immunology; Chemokines - metabolism; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1; Humans; Lymphocyte Activation - immunology; Receptors, CCR5 - biosynthesis; Receptors, Chemokine - biosynthesis; Receptors, HIV - metabolism; Signal Transduction; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80583-X

The history of chemokines can be traced back as far as 1977 with the characterization of platelet factor 4, although the prototypical chemokine IL-8 was not described until 1987. Identification of other structurally related chemotactic cytokines quickly followed with advances in molecular cloning techniques and availability of bioinformatics-based analyses of nucleotide databases. During the last 10 years, it has become apparent that chemokines are a large superfamily consisting of four subfamilies that display between two and four highly conserved NH sub(2)-terminal cysteine amino acid residues. The CXC (or alpha ) family has the first two NH sub(2)-terminal cysteines separated by one nonconserved amino acid residue. In contrast, the CC (or beta ) family has these cysteines in juxtaposition, and the C (or gamma ) family has one lone NH sub(2)-terminal cysteine residue, while the CX sub(3)C (or delta ) family has these cysteines separated by three intervening amino acids. There are now well over 40 characterized chemokines (some of which are listed in Table 1 and Table 2) as well as a number of virally encoded chemokine-like proteins, so this family far outnumbers other cytokine families. Most chemokines fall into the CXC and CC groups, since there is only one C and one CX sub(3)C chemokine known in human. The discovery of chemokine receptors also appears to be a modern growth industry. There are now at least 15 known chemokine receptors, many of which exhibit multiple ligand specificity, although the chemokine/ligand promiscuity does not usually cross CC versus CXC chemokine boundaries (Table 2). In addition, there are several orphan and virally encoded chemokine receptors, so the number of chemokine receptors will likely increase substantially over the next few years. Members of all four families are known to attract various subsets of T lymphocytes, and it is by virtue of their diversity that chemokines are ideal molecules for mediating a plethora of events such as selective trafficking of T lymphocyte subsets from intravascular to extravascular compartments, trafficking within lymph node and thymus, and/or recirculation from tissues to lymphatics. However, the large number of chemokines and their receptors, together with the expression of chemokine receptors on cells other than leukocytes (such as epithelial, endothelial, and smooth muscle cells), is probably indicative of the importance of these molecules in a wide range of biological functions. For e