POLYCLONAL B-CELL ACTIVATION-INDUCED BY HERPESVIRUS SAIMIRI-TRANSFORMED HUMAN CD4(-CELL CLONES - ROLE FOR MEMBRANE TNF-ALPHA() T)TNF-ALPHA RECEPTORS AND CD2/CD58 INTERACTIONS/

We have shown that in vitro infection with herpesvirus saimiri (HVS) c an transform human CD4(+) T cell clones with defined Th1 or Th2 cytoki ne profiles to continuous growth. We report here that transformation w ith HVS enabled both Th1 and Th2 clones to stimulate proliferation and Ig production by autologous or allogeneic B cells in the absence of s imulants. The polyclonal B cell-activating property of HVS-transformed clones was not related to free virus or soluble cytokines, but rather was dependent on an AG-nonspecific, MHC-unrestricted, contact-depende nt mechanism. T blasts from unstimulated HVS-transformed clones did no t express CD40 ligand (CD40L) mRNA or CD40L protein, whereas a proport ion of them constitutively expressed membrane TNF (mTNF)-alpha. Both C D40L and mTNF-alpha were detectable on either uninfected or HVS-transf ormed clones upon mitogen stimulation. The activation of high-density B cells by unstimulated HVS-transformed clones was not inhibited by so luble CD40-Ig fusion protein, but was strongly reduced by either anti- TNF-alpha or anti-TNF-alpha receptor (TNF-alpha R) mAbs. Addition of a nti-CD2 and/or anti-CD58 mAbs was also inhibitory, but no additive eff ect with anti-TNF-alpha and/or anti-TNF-alpha R mAbs was observed. Nei ther anti-IL-2 nor CD40-Ig inhibited the proliferation of naive IgD(+) B cells cocultured with fixed unstimulated HVS-transformed clones, wh ereas a combination of anti-TNF-alpha and anti-TNF-alpha R mAbs was in hibitory. In addition, fixed unstimulated HVS-transformed clones induc ed Ig synthesis in IgD(+) naive B cells even in the absence of exogeno us IL-2. Data suggest that both the mTNF-alpha/TNF-alpha R and the CD2 /CD58 pathways, but not the CD40L-CD40 interaction plus secreted cytok ines, are involved in the unusual mode of B cell activation exerted by CD4(+) HVS-transformed clones.