The chemokine receptor, CCR7 and interactions with its ligands CCL19 and CCL21 are well known to facilitate priming of T cells in lymphoid tissue. Our data demonstrate upregulation of CCR7, CCL19 and CCL21 in the brain during Toxoplasma gondii infection at a time point coincident with the peak of T cell infiltration in the CNS. CNS resident astrocytes significantly upregulate CCL21 following direct infection with Toxoplasma tachyzoites and in the absence of CCL21, plt/plt mice were less efficient in controlling parasite replication during chronic infection. Although T cells enter the infected brain in a CCR7 independent manner, migration of extravasated CD4+T cells from the perivascular area into the CNS parenchyma is CCL21-dependent. Our data also demonstrate accumulation of CD4+CCR7 expressing T cells in the infected brain. A significant proportion of these CCR7+T cells express memory T cell markers including IL-7R (Interleukin 7 Receptor) and CD103 (tissue resident memory phenotype). These data indicate CCR7-CCL21 interactions play a role in guiding CD4+CCR7+ memory T cell migration in the brain to prevent parasite reactivation and disease. Analysis of the behavior and phenotype of this memory T cell population in the absence of CCR7 or CCL21 will be presented. These data address the potential contribution of CCR7/CCL21 mediated interactions to maximize memory responses in the brain during Toxoplasma infection.
- Copyright © 2011 by The American Association of Immunologists, Inc.