||Objective: Plasma phospholipid transfer protein (PLTP) is a key determinant of lipoprotein metabolism, and both animal
and human studies converge to indicate that PLTP promotes atherogenesis and its thromboembolic complications.
Moreover, it has recently been reported that PLTP modulates inflammation and immune responses. Although earlier
studies from our group demonstrated that PLTP can modify macrophage activation, the implication of PLTP in the
modulation of T-cell-mediated immune responses has never been investigated and was therefore addressed in the present
study. Approach and results: In the present study, we demonstrated that PLTP deficiency in mice has a profound effect on
CD41 Th0 cell polarization, with a shift towards the anti-inflammatory Th2 phenotype under both normal and
pathological conditions. In a model of contact hypersensitivity, a significantly impaired response to skin sensitization
with the hapten-2,4-dinitrofluorobenzene (DNFB) was observed in PLTP-deficient mice compared to wild-type (WT)
mice. Interestingly, PLTP deficiency in mice exerted no effect on the counts of total white blood cells, lymphocytes,
granulocytes, or monocytes in the peripheral blood. Moreover, PLTP deficiency did not modify the amounts of CD41 and
CD81 T lymphocyte subsets. However, PLTP-deficiency, associated with upregulation of the Th2 phenotype, was
accompanied by a significant decrease in the production of the pro-Th1 cytokine interleukin 18 by accessory cells.
Conclusions: For the first time, this work reports a physiological role for PLTP in the polarization of CD41 T cells toward the pro-inflammatory Th1 phenotype.