Data are presented as mean SEM and are representative of one of two replicate experiments with 3 mice at each time point. mice during acute AS contamination by analyzing expression of the transcription factors T-bet and Foxp3. We also investigated if CXCR3 contributes to control MK-5046 of parasite replication and survival. The frequency and quantity of CD4+CXCR3+ T cells increased dramatically in the spleen of RCAN1 infected B6 mice coincident with increased CD4+IFN-+ T cells. CXCR3 was up-regulated on effector CD4+Foxp3? T cells as well as Foxp3+ Tregs. Consistent with our previous observations, CD4+T-bet+Foxp3? T cells increased in B6 mice during acute contamination. T-bet+Foxp3+ Tregs also increased significantly and a high frequency of these cells expressed CXCR3 supporting the notion that these cells may be Th1-like Tregs. Despite this, the percentage of CD4+Foxp3+ Tregs from infected B6 mice that migrated to the CXCR3 ligands CXCL9 and CXCL10 was significantly less than na?ve mice. To investigate the contribution of CXCR3 to control of acute blood-stage malaria, we compared the course and end result of AS contamination in wild-type (WT) B6 and CXCR3-deficient mice. Parasitemia levels were significantly higher around the time of peak parasitemia in CXCR3?/? compared to WT mice but survival was similar suggesting a role for CXCR3 in controlling parasite replication during acute AS infection. Together, our findings indicate Th1-like CD4+T-bet+Foxp3+ Tregs that express CXCR3 are induced during acute blood-stage malaria and suggest CXCR3 expression on CD4+ Th1 cells may contribute to their migration to the spleen. to identify the immune mechanisms required for protection against blood-stage contamination, important gaps in our knowledge remain. CD4+ T cell-B cell interactions are essential for control of parasite replication and removal of contamination (2). CD4+ Th1 cells that express T-bet and secrete IFN- and T follicular helper (Tfh) cells, crucial for generating antibody-mediated immunity, play important functions (2). Immunoregulatory mechanisms including the anti-inflammatory cytokine IL-10 and regulatory T cells (Tregs) are vital to safeguard the host from immunopathology and severe disease (3C5). On the other hand, such mechanisms may suppress protective immune responses. Although earlier studies on the role of CD4+Foxp3+ Tregs in immunity to malaria were not conclusive, recent findings in mice infected with AS or support the notion that Tregs suppress Th1 as well as Tfh cell responses (4, 6, 7). Indeed, higher blood parasitemia levels are associated with higher frequencies of CD4+Foxp3+ Tregs in humans and mice with malaria. Conversely, a lower frequency of Tregs is usually associated with better disease end result. During the acute phase of AS, C57BL/6 (B6) mice, used in the present study, have a significant increase in effector CD4+ Th1 cells that express T-bet and secrete IFN- (6, 8). The accumulation and growth of CD4+ Th1 cells that secrete IFN- in the spleen are essential for control and removal of AS contamination (9). Although CD4+Foxp3+ Tregs increase significantly in infected compared to na?ve B6 mice, there is a high ratio of effector CD4+ T cells to Tregs in these hosts during acute AS contamination (6). The lymphocyte-specific chemokine receptor CXCR3 expressed by activated T cells as well as NK cells is usually important for CD4+ Th1 cell migration to sites of inflammation and contamination (10, 11). Conversation of CXCR3 with its ligands, the C-X-C chemokines CXCL9 (monokine induced by MK-5046 IFN-), CXCL10 (interferon-induced protein-10), and CXCL11 (interferon-inducible T-cell alpha chemoattractant) MK-5046 contributes to Th1 cell differentiation (12). The MK-5046 C-X-C chemokines are induced by IFN- and are produced by several immune cells including macrophages and dendritic cells as well as non-immune cells..