Effector function of diabetogenic CD4 Th1 T cell clones: a central role for TNF-alpha.

Cell Clones: A Central Role for TNF- Effector Function of Diabetogenic CD4 Th1 T

T-bet down-modulation in tolerized Th1 effector CD4 cells confers a TCR-distal signaling defect that selectively impairs IFN-gamma expression.

When Th1 effector CD4 cells encounter tolerizing Ag in vivo, their capacity to express the effector cytokines IFN-gamma and TNF-alpha is lost more rapidly than noneffector functions such as IL-2 production and proliferation. To localize the relevant intracellular signaling defects, cytokine expression was compared following restimulation with Ag vs agents that bypass TCR-proximal signaling. IFN...

Polyclonal B cell activation induced by herpesvirus saimiri-transformed human CD4+ T cell clones. Role for membrane TNF-alpha/TNF-alpha receptors and CD2/CD58 interactions.

We have shown that in vitro infection herpesvirus saimiri (HVS) can transform human CD4+ T cell clones with defined Th1 or Th2 cytokine profiles to continuous growth. We report here that transformation with HVS enabled both Th1 and Th2 clones to stimulate proliferation and Ig production by autologous or allogeneic B cells in the absence of stimulants. The polyclonal B cell-activating property o...

Clonal analysis of functionally distinct human CD4+ T cell subsets

A large number of CD4+ T cell clones, obtained from peripheral blood T lymphocytes by direct limiting dilution, allowed us to address the question whether functional heterogeneity exists within the human CD4+ T cell subset. Cytotoxic capacity of cloned T cells was analyzed with the use of anti-CD3 antibodies and target cells bearing FcR for murine IgG. 6 of 12 CD4+ clones obtained were able to ...

Anti-human cytomegalovirus activity of cytokines produced by CD4+ T-cell clones specifically activated by IE1 peptides in vitro.

The control of latent cytomegalovirus (CMV) infections by the immune system is poorly understood. We have previously shown that CD4+ T cells specific for the human CMV major regulatory protein IE1 are frequent in latently infected healthy blood donors. In order to learn about the possible role of these cells, we have developed IE1-specific CD4+ T-cell clones and, in this study, analyzed their e...