CD30/CD30L is critical for Tfh cell differentiation and promotes antibody production against Plasmodium yoelii infection
Host resistance to malaria parasite infection relies on the establishment of a moderate and sequential adaptive immune response. The production of specific antibodies is critical for parasite clearance. CD30 and CD30L are respective members of the tumor necrosis factor (TNF) receptor superfamily and TNF superfamily; and are expressed on the surface of various immune cells and tissue cells. In mice infected with a non-lethal Plasmodium yoelii strain, CD30/CD30L expression was significantly increased. Using CD30L-deficient (CD30L-/-) mice, we found that the CD30/CD30L interaction played a crucial role in the activation of T follicular helper (Tfh) cells and germinal center (GC) B cells. During P. yoelii infection, CD30L-/- mice developed a weaker humoral response with reduced differentiation of Tfh cells, decreased secretion of IL-21, impaired formation of GCs, a lower number of antibody-secreting cells, and reduced production of antibodies. Supplementing the CD30L-/- mice with recombinant IL-21 (rIL-21) restored the number and proliferation of Tfh cells, but it did not completely restore the humoral immune response. The expression of IL-21R on CD4+ T cells and B cells in CD30L-/- mice during infection was significantly lower than that in wild-type mice; and supplementation with rIL-21 did not increase IL-21R expression on T and B cells. Therefore, we conclude that the CD30/CD30L receptor-ligand pair are key molecules for Tfh cell differentiation and maintenance of the Tfh-GC B cell response, which are needed for the establishment of humoral immunity against P. yoelii blood-stage infection. Overall design: We used transcriptomic data analysis to examine the key shifts in genetic signatures that derail the immune states in the absence of the CD30/CD30L signaling pathway.We performed gene expression profiling analysis using data obtained from RNA-seq of two groups, WT and CD30L-/- at day 10 post infection. Each group has 3 mice.