PMA alone induces proliferation of some murine T cell clones but not others

The responses of cloned murine T cell lines to the phorbol ester, phorbol myristate acetate (PMA), were investigated. PMA alone was able to stimulate proliferation of some clones but not others. Two Lyt-2+, cloned cytolytic T lymphocyte (CTL) lines proliferated in response to stimulation by PMA alone, but several L3T4+, cloned helper T lymphocyte (HTL) lines did not. In contrast, all clones tested released lymphokines in response to stimulation by the combination of PMA and the calcium ionophore A23187. Moreover, all clones proliferated in response to stimulation by the combination of PMA and A23187. The proliferation of HTL in response to PMA + A23187 could be completely inhibited either by cyclosporine A (CsA) or by PC61.5, a monoclonal antibody directed against the murine IL 2 receptor; however, the proliferation of CTL in response to PMA alone was not affected either by CsA or by PC61.5. These results suggest that of the murine T cell clones tested, HTL proliferate in response to stimulation via an IL 2-dependent, autocrine pathway; in contrast, CTL, in addition to an IL 2-dependent pathway, may possess an additional IL 2-independent pathway of proliferation. CTL that proliferate in response to stimulation by PMA alone may be useful models in the study of T cell proliferation.     

Interleukin 2 inhibits antigen-stimulated lymphokine synthesis in helper T cells by inhibiting calcium-dependent signalling

Certain L3T4+, Lyt-2- cloned murine helper T lymphocytes (HTL), when cultured with a high concentration of interleukin 2 (IL 2), become temporarily unresponsive to antigenic stimulation, as indicated by failure to proliferate and by reduced secretion of lymphokines when challenged with antigen. Exposure of cloned HTL to IL 2 also renders these cells less responsive to concanavalin A (Con A). Here we demonstrate that antigen-unresponsive HTL also accumulate reduced levels of lymphokine mRNA, thus indicating a pretranslational block of the response to antigen. However, HTL which had been pretreated with IL 2 and were unresponsive to antigen responded strongly to antigen + A23187 or to A23187 + PMA but failed to respond to antigen + PMA. With HTL made unresponsive to antigen or to Con A by exposure to IL 2, increases in intracellular calcium ion levels stimulated by Con A also were reduced. Thus, for mouse HTL clones, the IL 2-induced state of unresponsiveness to antigen or Con A appears to reflect an inability of such HTL to increase intracellular free calcium to a level sufficient for activation of lymphokine genes.     

Short-term effect on growth of two doses of GRF 1-44 in children with growth hormone deficiency: comparison with growth induced by methionyl-GH administration

In a double-blind study 12 prepubertal children with idiopathic growth hormone (GH) deficiency were treated with growth hormone releasing factor (GRF) 1-44 in a dosage of 7.5 or 15 micrograms/kg body weight, administered once a day subcutaneously. With 7.5 micrograms/kg the average growth velocity increased from 2.5 to 4.6 cm/year, an insufficient response. With the higher dosage the average growth velocity increased from 2.7 to 7.0 cm/year, a similar increase as observed with GH therapy in subsequent periods. In 3 of the 6 children treated with the higher dose appropriate catch-up growth was observed. The growth response of the lower leg length was not always consistent with the statural growth response.     

Islet cell antibodies, circulating immune complexes and antinuclear antibodies in diabetes mellitus

Serum samples of patients suffering from diabetes mellitus were tested for complement-fixing and non complement-fixing islet cell antibodies, antinuclear antibodies and circulating immune complexes. There was no correlation between circulating immune complexes or antinuclear antibodies and secondary diabetic complications. A close relationship was found between the ICA titer and complement fixation of ICA. The incidence of ICA at the onset of the disease was higher in the patients under the age of 10 (85%) and decreased with increasing age up to 45% in patients with onset above age 20. In five patients being positive and four patients being negative for ICA at onset of disease, changes and fluctuations in antibody titers were observed over 38 months. Since manifestation of diabetes mellitus is believed to be an endpoint of a long lasting autoimmune process, our observations indicate that the autoimmune phenomena are merely indicators of ongoing autoimmune reactions not necessarily reflecting the state of autoaggression or islet cell destruction.