Differential IL-2 expression defines developmental fates of follicular versus nonfollicular helper T cells.

DiToro, Daniel; Winstead, Colleen J; Pham, Duy; Witte, Steven; Andargachew, Rakieb; Singer, Jeffrey R; Wilson, C Garrett; Zindl, Carlene L et al. · Science · 2018

basic_science · Level V

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Abstract

In response to infection, naïve CD4<sup>+</sup> T cells differentiate into two subpopulations: T follicular helper (T<sub>FH</sub>) cells, which support B cell antibody production, and non-T<sub>FH</sub> cells, which enhance innate immune cell functions. Interleukin-2 (IL-2), the major cytokine produced by naïve T cells, plays an important role in the developmental divergence of these populations. However, the relationship between IL-2 production and fate determination remains unclear. Using reporter mice, we found that differential production of IL-2 by naïve CD4<sup>+</sup> T cells defined precursors fated for different immune functions. IL-2 producers, which were fated to become T<sub>FH</sub> cells, delivered IL-2 to nonproducers destined to become non-T<sub>FH</sub> cells. Because IL-2 production was limited to cells receiving the strongest T cell receptor (TCR) signals, a direct link between TCR-signal strength, IL-2 production, and T cell fate determination has been established.

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