Antigen-driven murine CD4+ T lymphocyte proliferation and interleukin-2 production are diminished by dietary (n-3) polyunsaturated fatty acids.

This study is the first to describe the impact of consuming a diet rich in (n-3) polyunsaturated fatty acids (PUFA) from fish oil on antigen-driven activation of naive CD4+ T lymphocytes. To accomplish this, we used lymphocytes isolated from T cell receptor (TCR) transgenic mice (i.e., DO11.10). A large portion of the T lymphocytes from these mice expresses a TCR specific for a peptide within the ovalbumin (OVA) molecule (OVA(323-339)). When this antigen is presented in the context of major histocompatibility complex I-A(d) with costimulation, these naive CD4+ T cells become activated, produce interleukin (IL)-2 and clonally expand. (n-3) PUFA enrichment was accomplished by feeding DO11.10 mice one of two nutritionally complete experimental diets that differed only in the source of fat: lard or menhaden fish oil [high in (n-3) PUFA]. After 2 wk of consuming the experimental diets, lymphocytes were isolated from the spleen of each mouse, then cultured in the presence of antigen (i.e., OVA(323-339)) or concanavalin A (Con A), a nonspecific, polyclonal T cell stimulus. IL-2 production and lymphocyte proliferation were determined after 48 and 72 h, respectively. Naive CD4+ T lymphocytes from fish oil-fed mice stimulated with antigen produced less IL-2 ( approximately 33%; P < 0.001) and proliferated to a lesser extent ( approximately 50%; P < 0.0001) than the same cells from lard-fed DO11.10 mice. When stimulated with Con A, (n-3) PUFA did not affect either proliferation or IL-2 production. In summary, we report for the first time that feeding mice a diet enriched with (n-3) PUFA reduces in vitro antigen-stimulated production of IL-2 and subsequent proliferation of naive CD4+ T lymphocytes.