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Cellular immunity changes caused by LDH virus: Analogy with observations on neuroblastoma-bearing mice

✍ Scribed by Georges Leclercq; Jean Willems; Hubertine Heremans; Jean-Paul Coutelier; Alfons Billiau; Marcel Joniau


Publisher
John Wiley and Sons
Year
1987
Tongue
French
Weight
706 KB
Volume
40
Category
Article
ISSN
0020-7136

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✦ Synopsis


Evidence is presented that LDH virus infection of mice results in drastic changes in several immune activities. Serum I F N titer and splenic N K activity are increased during the acute phase of infection. NK stimulation is mediated by IFN-C Y , ~ since injection of an antibody against murine IFN-a,P is able to abolish the effect. IL-2 production is inhibited throughout the study period following injection of LDH virus (14 days), although a partial recovery is observed during the second week. Similarly, IL-2 receptor expression and MLC responsiveness are suppressed. This suppression lasts for 2 and 7 days respectively after injection. Addition of recombinant IL-2, but not of indomethacin, to the MLC cultures restores the proliferation rate. Not only proliferation but also cytotoxic cell generation in MLC is diminished during the first week after LDH virus injection. Again, this response is normalized at day 14. Additional observations indicate that LDH virus is present in murine neuroblastoma. This explains some of the previously described effects of this tumor on the cellular immune system of the host.

from K.U. Leuven (Belgium), were bred in our laboratory. NMRI mice were obtained from the Experimental Animal Centre of the University of Leuven. NMRI mice were only used for interferon assays. For our experiments, 7-to 9-weekold mice of both sexes were used. Mice were found not to be contaminated with LDH virus, as determined from plasma LDH levels.

NB tumor

C1300 NB tumor, obtained from the Jackson Laboratories (Bar Harbor, ME), is maintained in vivo by serial intramuscular injections in the thigh (at 10-day intervals) of 5 X 10' viable tumor cells. Alternatively, NB cells are cultured in vitro before inoculation. The medium used is Eagle's minimal essential medium (EMEM) supplemented with non-essential amino acids, Earle's salts, 100 IU/ml penicillin, 100 pg/ml streptomycin, 2 mM L-glutamine, 2 g/l NaHC03 and 10% FCS (all from GIBCO. Irvine. Scotland). Tumors induced by these '2 methods will be called respectively "in vivo " and "in In human cancer patients, changes have been documented vitro ,, NB variants, When indicated, 3-5 106 PEC from concerning virtually every component of the immune system mice Were added twice a week to 5-ml cultures of NB (Ninnemann, 1978: Snyderman et al., 1977; Spina et ul.. 1981). These changes are thought to play a major role in Ce1I:free tumor supernatant oncogenesis. in the progression of metastases, and in the NB tumor cells were obtained by mincing dissected tumor increased susceptibility of cancer patients to intercurrent infec-fragments in PBS, ~f~~~ centrifugation (5 min, 500 g), the cell tions. Therefore, the results of in vivo and in vitro imniunolog-pellet was suspended in 40 vol of PBS. After centrifugation ical tests are often used as important diagnostic and prognostic for 5 min at 500 g, the supernatant was clarified by centrifuindices for a variety of human cancers (Catalona and ChrCtien. gation for min at 1