Lymphotoxin alpha beta is expressed on recently activated naive and Th1-like CD4 cells but is down-regulated by IL-4 during Th2 differentiation

Lymphotoxin (LT) is a cytokine that orchestrates lymphoid neogenesis and fo rmation of germinal center reactions, LT exists as a membrane heterotrimer of alpha and beta subunits and is secreted as a homotrimer, LT alpha 3, Usi ng LT beta R.Fc, expression of LT alpha beta on CD4 T cell subsets was inve stigated in a TCR transgenic model, LT alpha beta was evident 24-72 h after activation of naive T cells with specific Ag, and declined thereafter. Ear ly expression was independent of IFN-gamma and IL-12, however, IL-12 prolon ged expression. LT alpha beta was reinduced within 2-4 h after Ag restimula tion, but declined by 24 h regardless of IL-12 or IFN-gamma priming. Exposu re of naive T cells to IL-4 did not affect early LT alpha beta expression a t 24 h, but resulted in subsequent down-regulation. IL-4-differentiated Th2 effecters did not re-express LT alpha beta, and LT alpha beta was transien tly found on Th1 clones but not Th2 clones, LT alpha 3 and TNF were immunop recipitated from supernatants and lysates of IL-12 primed cells but not IL- 4 primed cells. These studies demonstrate that LT alpha beta is expressed b y activated naive CD4 cells, unpolarized IL-2-secreting effecters, and Th1 effecters. In contrast, loss of surface LT alpha beta and a lack of LT alph a 3 and TNF secretion is associated with prior exposure to IL-4 and a Th2 p henotype.