Receptor-directed focusing of lymphokine release by helper T cells

Abstract

The interaction between helper T cells and B cells, leading to the production of antibody to thymus-dependent antigens, was the first cell interaction clearly defined in the immune system^1–3; it remains both paradigmatic and controversial. Two requirements of this interaction, that the helper cell (T_H) and the B cell must recognize antigenic determinants that are physically linked^4,5, and that the T_H and the B cell must share genes encoding major histocompati-bility complex (MHC) class II molecules⁶, led to the concept that T_H–B interaction required an intimate physical association of the two cell types. But in vitro studies have shown that T_H can be replaced by soluble, antigen-nonspecific factors, capable of activating any B cell to secrete antibody^7,8. We have previously proposed that the requirements for T_H–B contact might result from T_H cells releasing their lymphokines in a polar fashion directed at that portion of the cell membrane where T-cell receptor cross-linking is actually occurring^9–16. Using an artificial monolayer of a cloned helper T-cell line, we show that lymphokines are r eleased preferentially over the area of receptor cross-linking under conditions of limited T_H-cell activation. Thus, it appears that one important aspect of the specificity of T_H–B cell interactions is the receptor-directed polar release of helper lymphokines.