Naive Human CD4+ T Cells Are a Major Source of Lymphotoxin α

Abstract

It is generally accepted that immunologically naive T cells display a very restricted cytokine production profile consisting mainly of IL-2, which is used as an autocrine growth factor. Here we report that activated naive CD4+ T cells, of neonatal or adult origin, express very high levels of soluble lymphotoxin (LT) α (LTα3), as determined by ELISA, RNase protection assay, and intracytoplasmic staining. Besides LTα3 and IL-2, these cells also produce high levels of TNF-α together with significant amounts of IFN-γ and IL-13. Naive cells also express LTβ mRNA and the membrane form of LTα (LTαβ). On average, naive CD4+ T cells secrete four times more LTα3 than Th1-like cells, twice more than naive CD8+ T cells, and ten times more than B cells. Thus, naive T cells express a large spectrum of cytokines, mainly of the Th1 type, and the very high levels of LTα3/TNF-α that they release may play an hitherto unsuspected role in the early stage of T cell-dependent immune responses.