CXCR3 directs antigen-specific effector CD4+ T cell migration to the lung during parainfluenza virus infection.
Effector T cells are a crucial component of the adaptive immune response to respiratory virus infections. Although it was previously reported that the chemokine receptors CCR5 and CXCR3 affect trafficking of respiratory virus-specific CD8+ T cells, it is unclear whether these receptors govern effector CD4+ T cell migration to the lungs. To assess the role of CCR5 and CXCR3 in vivo, we directly compared the migration of Ag-specific wild-type and chemokine receptor-deficient effector T cells in mixed bone marrow chimeric mice during a parainfluenza virus infection. CXCR3-deficient effector CD4+ T cells were 5- to 10-fold less efficient at migrating to the lung compared with wild-type cells, whereas CCR5-deficient effector T cells were not impaired in their migration to the lung. In contrast to its role in trafficking, CXCR3 had no impact on effector CD4+ T cell proliferation, phenotype, or function in any of the tissues examined. These findings demonstrate that CXCR3 controls virus-specific effector CD4+ T cell migration in vivo, and suggest that blocking CXCR3-mediated recruitment may limit T cell-induced immunopathology during respiratory virus infections.
Kohlmeier
Jacob E
JE
Trudeau Institute, Saranac Lake, NY 12983, USA.
Cookenham
Tres
T
Miller
Shannon C
SC
Roberts
Alan D
AD
Christensen
Jan P
JP
Thomsen
Allan R
AR
Woodland
David L
DL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019713:Receptors, CCR5 / Q000172:deficiency / Q000502:physiology; D054367:Receptors, CXCR3 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D010253:Respirovirus Infections / Q000276:immunology* / Q000473:pathology; D029082:Sendai virus / Q000276:immunology
C515188:Cxcr3 protein, mouse; D018984:Epitopes, T-Lymphocyte; D019713:Receptors, CCR5; D054367:Receptors, CXCR3