Human cell lines of hematopoietic origin were tested for production of tumor necrosis factor (TNF) hTNF activity was not found in supernatants of cell lines of T-cell, monocytic, or promyelocytic origin. Partially purified hTNF has a molecular weight of approximately 70,000, has no interferon activity, is acid labile, is destroyed by heating at 70°C for 1 hr, induces cross-resistance to mouse TNF in vitro, and causes hemorrhagic necrosis of Meth A mouse sarcoma in the standard in vivo mouse TNF assay. Tests with a panel of 23 human cancer cell lines showed that hTNF is cytotoxic for 7 cell lines, cytostatic for 5, and has no effect on 11. Comparative studies with human a, fi, and y interferons indicated that sensitivity to hTNF and interferon can be distinguished. Combined treatment with hTNF and a or y interferon resulted in a synergistic cytotoxic effect.

125I-labeled TNF(LuKII) (tumor necrosis factor) binds specifically to human and mouse cell lines sensitive to the cytotoxic effect of TNF, but not to cells made resistant to TNF. TNF-sensitive cells have cell surface receptors with a high affinity for TNF(LuKII). Mouse TNF competes with TNF(LuKII) for receptor binding. Scatchard analysis of the binding data yielded linear plots and suggests that TNF(LuKII) binds to homogeneous receptor sites. The number of TNF(LuKII) receptors on two TNF-sensitive cell lines is 200-300 per cell and the affinity constant of the receptor for TNF(LuKII) is approximately 1 X 10(-10) M.

T‐cell responses against soluble antigens, alloantigens and mitogens are frequently diminished in patients with certain types of cancer. In the present study, the authors investigated possible mechanisms for the partial T‐cell immunodeficiency in patients with Hodgkin's or non‐Hodgkin's lymphomas. It was found that T‐cells from lymphoma patients had significantly reduced proliferative responses to EBV‐transformed B‐cell lines and to anti‐TCR/CD3 MoAb; a 30–50% reduction of cells expressing membrane T‐cell receptor (TCR) complexes; and a significantly reduced signal transduction function. Long‐term in vitro culture conditions were developed to expand T cells in TCR/CD3‐dependent or TCR/CD3‐independent manners. With such methods, it was found that the decreased T‐cell responses in patients with Hodgkin's and non‐Hodgkin's lymphomas appeared to be an intrinsic T‐cell defect (not at the antigen presenting cell level), and the T‐cell responses could be recovered after only a few days in culture. Thus, it is suggested that the T‐cell response–defect in Hodgkin or non‐Hodgkin lymphoma patients is a reversible phenomenon, dependent on the patient's tumour‐bearing environment.

No abstract

During the first 2 to 4 weeks of progressive visceral infection with the intracellular protozoan, Leishmania donovani, spleen cells from BALB/c mice failed in response to leishmanial antigen to produce either of the activating T cell-derived lymphokines, interleukin 2 (IL 2) or gamma-interferon (IFN-gamma). Four weeks after infection, however, antigen-induced IL 2 and IFN-gamma secretion emerged and coincided with the onset of control over parasite replication and the subsequent killing of greater than 80% of intrahepatic L. donovani. The development of this immunosecretory activity correlated with the hepatic tissue response at the site of parasitized Kupffer cells. This response progressed from Kupffer cell fusion (week 1) to fusion plus a mononuclear cell infiltrate (week 2) to well-organized granuloma formation (weeks 4 to 8). In contrast, T cell-deficient nude BALB/c mice exerted no control over L. donovani, their spleen cells failed to generate antigen-induced IFN-gamma, and at 4 weeks, their livers were devoid of any tissue reaction. Since spleen cells from 2-week infected normal mice did not produce antigen-stimulated IL 2 or IFN-gamma, these mice were treated with recombinant (r) lymphokines. Various protocols using both high and low dose human rIL 2 had no antileishmanial effect. Hepatic parasite replication was completely halted, however, by macrophage-activating doses of murine rIFN-gamma. These results reemphasize that an intact T cell-dependent response is required for successful defense against L. donovani, indicate that this immune response can be measured at both the cellular (secretory) and tissue levels, and confirm that IFN-gamma can exert an antileishmanial effect in vivo.