CD4+ T helper cells can protect against many infectious agents, including malaria parasites. The T-helper-1 (Th1) subset, for example, can protect by boosting the antimicrobial activity of phagocytes via IFNγ. Discovery of mechanisms controlling Th1 differentiation may offer opportunities for improving immunity to many pathogens. Previously, we observed early co-expression of chemokine receptors CXCR3 and CXCR5 by Plasmodium-specific TCR transgenic PbTII cells in P.chabaudi-infected mice, prior to their bifurcation towards either Th1 or T follicular helper (Tfh) fate [1]. We hypothesized here that early competition between CXCR3 and CXCR5 influenced Th1/Tfh fate. To test this, genes encoding CXCR3, CXCR5, or CXCR6 were disrupted in naïve PbTIIs via CRISPR/Cas9 and examined for effects on differentiation in vivo. None of these chemokine receptors, either alone or in combination, substantially influenced either PbTII expansion or Th1-differentiation, while interactions via LFA-1, or IL-2-signalling via CD25 were required for optimal clonal expansion and Th1 differentiation. In addition, consistent with our spatial transcriptomic analysis, which suggested a role for monocyte-Th1 interactions via CCR5, CRISPR/Cas9-mediated disruption of Ccr5 reduced clonal expansion and Th1-differentiation in our model. Hence, we propose that CCR5-dependent monocytic-interactions of IL-2-primed CD4+ T cells promotes Th1 immunity in malaria. These data provide mechanistic insight into how Th1-reponses are optimally generated in vivo.