CC Chemokine Ligand 3 (CCL3) Regulates CD8+-T-Cell Effector Function and Migration following Viral Infection

AUTOR(ES)

Trifilo, Matthew J.

FONTE

American Society for Microbiology

RESUMO

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 CD44high, they remained CD62Lhigh and CD25low, 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.

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