Oleic acid enhances proliferation and calcium mobilization of CD3/CD28 activated CD4⁺ T cells through incorporation into membrane lipids

Unsaturated fatty acids (UFA) are crucial for T‐cell effector functions, as they can affect the growth, differentiation, survival, and function of T cells. Nonetheless, the mechanisms by which UFA affects T‐cell behavior are ill‐defined. Therefore, we analyzed the processing of oleic acid, a prominent UFA abundantly present in blood, adipocytes, and the fat pads surrounding lymph nodes, in CD4 + T cells. We found that exogenous oleic acid increases proliferation and enhances the calcium flux response upon CD3/CD28 activation. By using a variety of techniques, we found that the incorporation of oleic acid into membrane lipids, rather than regulation of cellular metabolism or TCR expression, is essential for its effects on CD4 + T cells. These results provide novel insights into the mechanism through which exogenous oleic acid enhances CD4 + T‐cell function.