Recent studies by my lab and others have first identified a novel population of CD8+ T cells using animal models and samples from human immunodeficiency virus (HIV)-infected humans and simian immunodeficiency (SIV)-infected monkeys. This subset, termed as follicular cytotoxic T (Tfc) cells, is shown to control viral infections within B-cell follicles. It is also evident that transcription factors (TFs) including Bcl6, Blimp1 and TCF-1, which have been reported to modulate follicular helper T (Tfh) cells, were also key TFs shaping Tfc differentiation. However, it remains elusive how Tfc cell fate is initiated by extracellular signals, particularly by environmental cytokine milieu. During my PhD study, I set up the mouse model of lymphocytic choriomeningitis virus (LCMV) infection, where effector CD8+ T cells can upregulate CXCR5 and migrate into B-cell follicles. Taking the advantage of this model, I examined several candidate cytokines and found that IL-2 treatment specifically inhibited Tfc differentiation and their Bcl6 expression. Fluorescence staining confirmed again the limited entry of CD8+ T cells into the follicles. Overexpression of STAT5, the downstream molecule stimulated by IL-2 signal, in LCMV-specific CD8+ (P14) T cells also significantly dampened Tfc formation. Interestingly, the inhibition by IL-2-STAT5 axis on Tfc cells can be Blimp1-independent as in Blimp1-deficient mice, Tfc differentiation was also inhibited by IL-2 treatment. On the other hand, however, IL-12 represents a promising candidate to enhance the generation of Tfc cells. To conclude, this study provides new insights into cytokines that guide the differentiation and function of Tfc subsets, paving the way to design new strategies to treat chronic viral infections such HIV.