T‐bet modulates the antibody response and immune protection during murine malaria

CD4⁺ T‐cell subtypes govern the synthesis of different Ab isotypes and other immune functions. The influence of CD4⁺ T‐cell differentiation programs on isotype switching and other aspects of host immunological networks during malaria infection are currently poorly understood. Here, we used Tbx21^?/? mice deficient for T‐bet, a regulator of Th1 CD4⁺ T‐cell differentiation, to examine the effect of Th1 CD4⁺ T cells on the immune protection to nonlethal murine malaria Plasmodium yoelii 17XNL. We found that Tbx21^?/? mice exhibited significantly lower parasite burden that correlated with elevated levels of IgG1, indicating that T‐bet‐dependent Ab isotype switching may be responsible for lower parasite burden. Absence of T‐bet was also associated with a transient but significant loss of T cells during the infection, suggesting that T‐bet may suppress malaria‐induced apoptosis or induce proliferation of T cells. However, Tbx21^?/? mice produced greater numbers of Foxp3⁺CD25⁺ regulatory CD4⁺ T cells, which may contribute to the early contraction of T cells. Lastly, Tbx21^?/? mice exhibited unimpaired production of IFN‐γ by a diverse repertoire of immune cell subsets and a selective expansion of IFN‐γ‐producing T cells. These observations may have implications in malaria vaccine design.