A human suppressor T cell clone which recognizes an autologous helper T cell clone.

In contrast to the many reports of IL-2 dependent proliferating, helper or killer cell clones, there is only a single report of an IL-2 dependent suppressor cell clone, in the mouse. However by the same cloning procedures used to generate human helper cells, suppressor cell clones to influenza virus could not be generated, and so another strategy was used. Jerne's network hypothesis proposes that immune regulation results from lymphoid cell receptors recognizing determinants on other lymphoid cell receptors. If this is the case it should be possible to generate regulatory T cell clones against other T cells and we report here the generation of an autologous suppressor cell clone which recognizes and inhibits the function of a human helper T cell clone. Such an autologous suppressor cell clone provides a new approach to understanding the pathways and molecular events involved in immune regulation. Mutual stimulation of the suppressor cell clone and the target helper cell clone in the absence of back stimulation, provides direct experimental evidence for the existence of interactions between T cell receptors, and thus suggests that the specificity of the suppressor cell clone is for the antigen receptor of the helper cell

Structure of a kinesin-tubulin complex and implications for kinesin motility

The typical function of kinesins is to transport cargo along microtubules. Binding of ATP to microtubule-attached motile kinesins leads to cargo displacement. To better understand the nature of the conformational changes that lead to the power stroke that moves a kinesin's load along a microtubule, we determined the X-ray structure of human kinesin-1 bound to αβ-tubulin. The structure defines the mechanism of microtubule-stimulated ATP hydrolysis, which releases the kinesin motor domain from microtubules. It also reveals the structural linkages that connect the ATP nucleotide to the kinesin neck linker, a 15-amino acid segment C terminal to the catalytic core of the motor domain, to result in the power stroke. ATP binding to the microtubule-bound kinesin favors neck-linker docking. This biases the attachment of kinesin's second head in the direction of the movement, thus initiating each of the steps taken

Insulin-Like Growth Factor-I (IGF-I) Enhances Immune Response in Dexamethasone-Treated or Surgically Stressed Rats Maintained with Total Parenteral Nutrition

Background: New evidence suggests that insulin-like growth factor-I (IGF-I) is an important regulator of immune response. Our objective was to determine the effects of IGF-I on immune response during total parenteral nutrition (TPN) using two stress models. Methods: Male, Sprague-Dawley rats (230 to 250 g) were given TPN with or without coinfusion of recombinant human IGF-I (800 μg/d for 6 days) and subjected to either dexamethasone, a synthetic glucocorticoid, or surgical stress, in the form of a midline abdominal incision. In the dexamethasone model, immune response was assessed by total cellularity of the thymus and spleen, in vitro assays of lymphocyte proliferation, and interleukin 6 (IL-6) production, and concentrations of IL-6 and tumor necrosis factor α (TNF-α) in serum. In the surgical model, flow cytometry was used to identify and quantify splenic populations of T and B lymphocytes and macrophages. Results: In rats immunosuppressed by dexamethasone, IGF-I infusion increased mitogen-induced proliferation of thymocytes, but did not alter cellularity in the thymus; enhanced proliferation and IL-6 production in peripheral blood mononuclear cells following treatment with concanavalin A or lipopolysaccharide; and reduced the serum concentration of IL-6, but not TNF-α. In surgically stressed rats, IGF-I infusion restored the splenic populations of immature and mature B lymphocytes, which were decreased by TPN. Conclusions: Our data demonstrate that IGF-I enhances immune response during TPN in rats. (Journal of Parenteral and Enteral Nutrition 19:444-452, 1995