CC chemokine ligand 3 (CCL3) regulates CD8(+)-T-cell effector function and migration following viral infection.
Chemokines induce the directional migration of targeted populations of leukocytes during periods of inflammation. Moreover, these molecules also regulate T-cell activation and differentiation following antigenic stimulation. In the present study, the contributions of the CC chemokine ligand 3 (CCL3) to the differentiation and migration of effector T cells in response to viral infection of the central nervous system (CNS) were analyzed. CCL3(-/-) mice infected with mouse hepatitis virus exhibited a significant reduction of virus-specific CD8(+) T cells within the CNS, correlating with delayed viral clearance. Decreased infiltration of CD8(+) T cells into infected CCL3(-/-) mice was associated with enhanced accumulation of primed CD8(+) T cells in cervical lymph nodes. Although virus-specific CD8(+) T cells from CCL3(-/-) mice were CD44(high), they remained CD62L(high) and CD25(low), retained CCR7 expression, and contained limited transcripts of the proinflammatory chemokine receptors CCR5 and CXCR3 compared with virus-specific CD8(+) T cells from CCL3(+/+) mice. Furthermore, the absence of CCL3 impaired the cytokine production and cytolytic activity of CD8(+) T cells. In addition, macrophage accumulation within the CNS was significantly decreased in infected CCL3(-/-) mice, correlating with reduced demyelination. These results suggest that CCL3 not only mediates macrophage chemotaxis but also significantly enhances differentiation of primed CD8(+) T cells into effector cells and their release into circulation, thus potentiating effective migration to the site of infection.
Trifilo
Matthew J
MJ
Department of Molecular Biology and Biochemistry, University of California, Irvine 92697-3900, USA.
Bergmann
Cornelia C
CC
Kuziel
William A
WA
Lane
Thomas E
TE
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002465:Cell Movement; D002493:Central Nervous System Diseases / Q000276:immunology / Q000821:virology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018352:Coronavirus Infections / Q000276:immunology* / Q000821:virology; D003711:Demyelinating Diseases / Q000209:etiology / Q000276:immunology / Q000821:virology; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000821:virology; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000276:immunology* / Q000472:pathogenicity; D010641:Phenotype; D015398:Signal Transduction
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D008024:Ligands; D019402:Macrophage Inflammatory Proteins