Control of differential CD4+ T lymphocyte behavior in vitro is dictated by the pattern of CD molecule involvement

ABSTRACT

T lymphocyte responses in vitro are not all-or-none choices to environmental stimulation, but follow at least three distinct patterns full activation and expansion, anergy induction, and receptor-mediated suicide by apoptosis. In vitro model systems were devised to investigate the differential control of T cell responses by surface CD activation molecules, CD4+ T cells from T. cruzi-infected mice are severely impaired in their proliferative response to TCR stimulation. TCR stimulation leads to CD4+ T cell suicide by apoptosis, but CD3 stimulation is less efficient in this effect. Triggering of normal CD4 T cells through CD4 coincident with TCR activation, does not affect proliferative responses, but induces marked morphological changes in the T cells, which become adherent, form extended cytoplasmic projections, and acquire motile behavior. This response requires IL4 production, and can be markedly upregulated by exogenous IL4. Autoreactive CD4 T cell functioning can help syngeneic B cells to produce a TH2 pattern of immunoglobulin isotypes following stimulation by a thymus independent antigen. These results indicate that distinct patterns of functional behavior in vitro can be induced, depending both on the past experience of the T cell and on the exact array of stimulatory CD antigens engaged in the process of activation. The relevance of these constraints in generating variable behavior for immunoregulation is discussed.