Human Germinal Center CD4+CD57+T Cells ActDifferently On B Cells Than Do Classical T-Helper Cells

摘要

We have isolated two subtypes of helper T cells from human tonsils: CD4+CD57+cells,mostly located in the germinal center (GC), and CD4+CD57-cells, distributed through theinterfollicular areas but also present in the GC. In a functional study, we have compared thecapacities of these T-cell subtypes to stimulate B cells in cocultures. In order to block T-cellproliferation while maintaining their activation level, we pretreated isolated T cells withmitomycin C prior to culture in the presence of B cells and added polyclonal activators suchas PHA and Con A, combined or not with IL-2. Contrary to CD4+CD57-cells,CD4+CD57+cells did not markedly enhance B-cell proliferation. Even when sIgD-B cellstypical of germinal center cells were tested, the CD4 CD57 cells had no significant effect.This is in accordance with the location of these cells: They mainly occupy the light zonesof the GC where few B cells divide. Even when added to preactivated, actively proliferatingcells, CD4+CD57+cells failed to modulate B-cell multiplication. On the supernatants ofB-cell-T-cell cocultures, we examined by the ELISA technique the effect of T cells on Igsynthesis. Contrary to CD57-T cells, whose effect was strong, CD57+T cells weaklystimulated Ig synthesis. More IgM than IgG was generally found. Because CD57 antigen isa typical marker of natural killer cells, we tested the cytolytic activity of tonsillarCD4+CD57+cells on K562 target cells. Unlike NK cells, neither CD4+CD57+norCD4+CD57-cells exhibit any cytotoxicity. Thus, germinal center CD4+CD57+cells are notcytolytic and do not strongly stimulate either B-cell proliferation or Ig secretion.CD4+CD57-cells, however, enhance B-cell proliferation and differentiation, thus actinglike the classical helper cells of the T-dependent areas.