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. 2025 Apr 11;222(7):e20241667. doi: 10.1084/jem.20241667

Figure 4.

Figure 4.

A single infection attenuates T cell activation. (A) The percentage of activated CD38hi effector or effector memory (EM) CD4+ T cells was analyzed by flow cytometry at baseline (grey dots) and 6 days after parasite clearance (colored dots) during the VAC063C study. Data are shown for volunteers undergoing their first, second, or third infection of life (see Fig. S2 B for gating strategies). (B) The percentage of activated CD38hi effector or effector memory CD4+ T cells at baseline (grey dots) and 6 days after parasite clearance (colored dots) during the VAC069 study. (C and D) RNAseq was used to identify differentially expressed genes in flow-sorted effector (effector memory) CD4+ T cells (T6 versus baseline) in first and third infection during VAC063C (adj P < 0.05 and >1.5 fold-change [FC]). The heatmaps in C show the log2 fold-change of markers of T cell activation and exhaustion and the master transcription factors that shape T cell fate. Non-significant genes are displayed with a log2 fold-change of zero and square brackets indicate that common protein names have been used. The stacked circular bar chart in D shows the log2 fold-change of cytokines and cytotoxic effector molecules. (E) Correlation between log10 transformed TRBV gene frequency at baseline and 28 days after challenge (convalescence) showing linear regression (black line) with 99% confidence intervals (grey shaded area). These data represent V gene usage across the entire T cell compartment and were obtained after one or two malaria episodes from volunteers who were subsequently infected for a third time during VAC063C. In A, n = 3 for the first infection, n = 2 for the second infection, and n = 6 for the third infection. In B, n = 8 for the first infection and n = 3 for the second infection. In C and D, n = 2 or 3 for the first infection (T6 and baseline, respectively) and n = 6 for the third infection (v313 was excluded at T6 because this sample failed QC). In E, n = 5 in the first and second infection (v1065 convalescence samples failed QC).