Production of α-lymphotoxin by human T-cell subsets

Abstract

Human T cells were isolated from peripheral blood lymphocytes (PBL) and sensitized to allogeneic PBL in a one-way mixed-lymphocyte culture. These sensitized T cells were fractionated on the basis of their possession of Fc receptors for IgG (T G+) or IgM (T M+), or the absence of both IgG and IgM receptors (T G−M−). When restimulated with alloantigen of the same derivation, T G+, T M+, and T G−M− cells yielded almost equal amounts of cytotoxin. Anti-α-lymphotoxin serum neutralized most of this cytotoxic activity indicating that α-lymphotoxin (α-LT) constituted most of this activity. Although T G−M− cells function as effectors in allogeneic cytotoxicity, T G+ cells lyse IgG-coated targets in an antibody-dependent cell-mediated cytotoxic (ADCC) reaction, which has been shown to be mediated in part by α-LT. Whether T M+ cells can be cytotoxic is not clear. In addition, freshly isolated human T-cell subsets were stimulated with phytohemagglutinin-P (PHA-P). After PHA stimulation, T G+, T M+, and T G−M− cells produced similar amounts of soluble cytotoxin, which was largely neutralized by anti-α-LT. The T G+ cells incorporated less thymidine than the T M+ or T G−M− cells. Likewise, OKT4+ and OKT8+ subsets, isolated with the aid of monoclonal OKT8 or OKT4 antibody and complement, yielded lymphotoxin after stimulation with PHA. It is shown that all T-cell subsets, as defined here, can produce lymphotoxin. Furthermore, depending on the assay system, cytotoxicity can be clearly demonstrated in all of these subsets, except in T M+ cells, where positive and negative results have been reported.