Gamma-globulin modulates growth of EBV-derived B-cell tumors in SCID mice reconstituted with human lymphocytes.
The effect of weekly gamma-globulin injection on the development of human B-cell tumors was studied in 120 mice with severe combined immunodeficiency (SCID). The mice were injected intraperitoneally (i.p.) with human peripheral mononuclear cells (PBMC) from 6 different Epstein-Barr virus (EBV)-seropositive donors. Animals repopulated with cells from 5 donors received gamma-globulin or saline for 20 weeks and were followed up to 24 weeks after reconstitution. A delay in the appearance of fata EBV-derived human B-cell tumors was noticed in the gamma-globulin-treated groups as compared to the controls. In a separate experiment, the effect of gamma-globulin treatment during the initial 4 weeks after reconstitution was compared to treatment from week 5 to week 8 as well as to a continuous 20-week treatment. The results from this experiment showed that B-cell tumor growth could be prevented just as efficiently when the animals were treated only during the first 4 weeks. In contrast, no preventive effect was seen when the first gamma-globulin dose was given at the beginning of week 5 after reconstitution. Our results indicate that gamma-globulin reduces the frequency of EBV-derived B-cell tumor development and suggest that SCID mice repopulated with human cells represent a useful in vivo model for evaluation of the prophylactic and/or therapeutic effects of immunomodulatory treatments in lympho-proliferative disorders associated with immunosuppression.
Abedi
M R
MR
Department of Clinical Immunology, Huddinge Hospital, Karolinska Institute, Sweden.
Christensson
B
B
al-Masud
S
S
Hammarström
L
L
Smith
C I
CI
D000818:Animals; D002455:Cell Division; D005455:Fluorescent Antibody Technique; D004854:Herpesvirus 4, Human; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism; D008214:Lymphocytes / Q000382:microbiology / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D013997:Time Factors; D005719:gamma-Globulins / Q000008:administration & dosage / Q000494:pharmacology*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D005719:gamma-Globulins