Chemokines: understanding their role in T-lymphocyte biology

The chemokines are a complex superfamily of small, secreted proteins that were initially characterized through their chemotactic effects on a variety of leucocytes. The superfamily is divided into families based on structural and genetic considerations and have been termed the CXC, CC, C and CX3C families. Chemokines from these families have a key role in the recruitment and function of T lymphocytes. Moreover, T lymphocytes have also been identified as a source of a number of chemokines. T lymphocytes also express most of the known CXC and CC chemokine receptors to an extent that depends on their state of activation/differentiation and/or the activating stimuli. The expression of two chemokine receptors, namely CXCR4 and CCR5, together with the regulated production of their respective ligands, appears to be extremely important in determining sensitivity of T cells to HIV-1 infection. The intracellular events which mediate the effects of chemokines, particularly those elicited by the CC chemokine RANTES, include activation of both G-protein- and protein tyrosine kinase-coupled signalling pathways. The present review describes our current understanding of the structure and expression of chemokines and their receptors, the effects of chemokines on T-cell function(s), the intracellular signalling pathways activated by chemokines and the role of certain chemokines and chemokine receptors in determining sensitivity to HIV-1 infection.