TRANSIENT EXPRESSION OF HUMAN INTERLEUKIN-2 AND INTERFERON-GAMMA GENES IS REGULATED BY INTERACTION BETWEEN DISTINCT CELL SUBSETS

The level of transient expression of human IL-2 and IFN-gamma genes, w e show, is regulated by dynamic interaction between two functionally d istinct cell populations. One is able to express these genes, while th e other, bearing one of several specific surface markers, actively inh ibits their expression. Defined cell subsets were isolated from PBMC a nd tonsil cells using immunomagnetic beads coated with monoclonal anti bodies directed against surface markers. Depletion of CD8, CD11a (Leu1 5), or Leu8 subsets led to a pronounced superinduction of IL-2 and IFN -gamma gene expression when the remaining cell population was stimulat ed with mitogen (PHA) or antigen (SEE). Thus, a 10-fold increase in pr oduction of IFN-gamma was observed after removal of CD11a (Leu15) cell s constituting only a small percentage of the total cell population. B y contrast, depletion of cells expressing CD19, a B cell marker, did n ot yield any superinduction. Conversely, CD8, CD11a (Leu15), or Leu8 c ell subsets, but not CD19 cells, each inhibited the induction of IL-2 and IFN-gamma gene expression almost completely in depleted or total c ell populations from which they were derived. Gene expression occurrin g within one cell subset could be effectively inhibited by cells from a second subset. Introduction of inhibitory cells (Leu8) into a popula tion that actively expressed IL-2 and IFN-gamma mRNA resulted in an im mediate cessation of gene expression. This suppression involves a solu ble mediator, since the culture medium in which such cells were activa ted exerted a similarly effective inhibition. (C) 1995 Academic Press, Inc.