Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes.
Several studies have shown that CC chemokines attract T lymphocytes, and that CD45RO+, memory phenotype cells are considered to be the main responders. The results, however, have often been contradictory and the role of lymphocyte activation and proliferation has remained unclear. Using CD45RO+ blood lymphocytes cultured under different stimulatory conditions, we have now studied chemotaxis as well as chemokine receptor expression. Expression of the RANTES/MIP-1 alpha receptor (CC-CKR1) and the MCP-1 receptor (CC-CKR2) was highly correlated with migration toward RANTES, MCP-1, and other CC chemokines, and was strictly dependent on the presence of IL-2 in the culture medium. Migration and receptor expression were rapidly downregulated when IL-2 was withdrawn, but were fully restored when IL-2 was added again. The effect of IL-2 could be partially mimicked by IL-4, IL-10, or IL-12, but not by IL-13, IFN gamma, IL-1 beta, TNF-alpha, or by exposure to anti-CD3, anti-CD28 or phytohemagglutinin. Activation of fully responsive lymphocytes through the TCR/CD3 complex and CD28 antigen actually had the opposite effect. It rapidly downregulated receptor expression and consequent migration even in the presence of IL-2. In contrast to the effects on CC chemokine receptors, stimulation of CD45RO+ T lymphocytes with IL-2 neither induced the expression of the CXC chemokine receptors, IL8-R1 and IL8-R2, nor chemotaxis to IL-8. The prominent role of IL-2 in CC chemokine responsiveness of lymphocytes suggests that IL-2-mediated expansion is a prerequisite for the recruitment of antigen-activated T cells into sites of immune and inflammatory reactions.
Loetscher
P
P
Theodor-Kocher Institute, University of Bern, Switzerland.
Seitz
M
M
Baggiolini
M
M
Moser
B
B
D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism* / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
C515334:CCR2 protein, human; D018106:CD28 Antigens; D017252:CD3 Complex; D018925:Chemokines; D007376:Interleukin-2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; C080633:macrophage inflammatory protein 1alpha receptor