title: Major histocompatibility complex class II-regulated immunity to murine leukemia virus protects against early T- but not late B-cell lymphomas.
abstract: We studied the relative importance of class I and class II major histocompatibility complex (MHC) immunoregulation in the control of T- and B-cell lymphomas induced by murine leukemia virus. Previously, we have described a mink cell focus-inducing (MCF) murine leukemia virus, MCF 1233, which induces not only lymphoblastic T-cell lymphomas but also follicle center cell or lymphoblastic B-cell lymphomas. We now report that the outcome of neonatal infection with MCF 1233 in H-2-congenic C57BL/10 and C57BL/6 mice is decisively influenced by the H-2 I-A locus. A total of 64% of H-2 I-Ak, d mice [B10.BR, B10.D2, B10.A(2R), B10.A(4R), and B10.MBR] developed T-cell lymphomas after MCF 1233 infection (mean latency, 37 weeks). In contrast, H-2 I-Ab [B10, B10.A(5R), B6], H-2 I-Ab/k [(B10.A x B10)F1 and (B10 x B10.A)F1], and H-2 I-Abm12 (bm12) mice were resistant against T-cell lymphomagenesis, but 65% of these H-2 I-Ab, b/k, bm12 animals developed B-cell lymphomas (mean latency, 71 weeks). Animals of T-cell lymphoma-susceptible strains that escaped from T-cell lymphomagenesis developed B-cell lymphomas with similar frequency as animals of T-cell lymphoma-resistant strains, but with a shorter latency. H-2 class II-determined regulation of antiviral immunity was reflected in the presence of high titers of antiviral envelope antibodies in T-cell lymphoma-resistant B-cell lymphoma-susceptible H-2 I-Ab, b/k, bm12 mice, whereas in T-cell lymphoma-susceptible H-2 I-Ak,d mice no antiviral antibodies were found. At week 4 after neonatal MCF 1233 infection, a high percentage of thymocytes were virally infected in both T-cell lymphoma-susceptible and -resistant mice. However, T-cell lymphoma-resistant animals cleared the thymic infection between weeks 4 and 10 of age, coinciding with a sharp rise in serum levels of antiviral antibodies. We conclude that the pleiotropic effects of MCF 1233 infection in H-2-congenic mice result from MHC class II I-A-determined T-cell response differences.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
authors.forename: W L
authors.initials: WL
authors.lastname: Vasmel
authors.forename: M
authors.initials: M
authors.lastname: Zijlstra
authors.forename: T
authors.initials: T
authors.lastname: Radaszkiewicz
authors.forename: C J
authors.initials: CJ
authors.lastname: Leupers
authors.forename: R E
authors.initials: RE
authors.lastname: de Goede
authors.forename: C J
authors.initials: CJ
authors.lastname: Melief
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000032:analysis; D001402:B-Lymphocytes; D001853:Bone Marrow / Q000382:microbiology; D004198:Disease Susceptibility; D005455:Fluorescent Antibody Technique; D005802:Genes, MHC Class II; D007113:Immunity, Innate; D009052:Leukemia Virus, Murine / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology; D008223:Lymphoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D008908:Mink Cell Focus-Inducing Viruses / Q000276:immunology* / Q000502:physiology; D013154:Spleen / Q000382:microbiology; D013601:T-Lymphocytes; D013950:Thymus Gland / Q000382:microbiology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral