Activation of natural killer cells by mouse mammary tumor virus C4 in BALB/c and T-cell receptor V beta 2-transgenic mice.
Lymphocytic infiltrates of BALB/c C4 hyperplastic alveolar nodule (HAN) have elevated natural killer (NK) activity, which correlates positively with the progression of C4 HAN to tumor: C4 HAN produces an infectious mouse mammary tumor virus, MMTV(C4), which encodes a superantigen that activates and deletes T-cells with the V beta 2 segment in the T-cell receptor. In this report, NK activation by both MMTV(C4) and MMTV(C4) superantigen was tested. NK activity was measured in naive BALB/c mice, BALB/c mice depleted of V beta 2+ T-cell, or V beta 2-transgenic mice after they received injections of either purified MMTV(C4) or MMTV(C4)-infected splenocytes. Elevated NK activity was observed in BALB/c mice receiving MMTV(C4) or MMTV(C4)-infected splenocytes. Depletion of V beta 2+, but not V beta 8+, T-cells by specific anti-V beta hybridoma before injection of MMTV(C4)-infected cells reduced but did not eliminate NK activation. NK activation in V beta 2-transgenic mice occurred before massive CD4 T-cell deletion took place and was more pronounced than that in the nontransgenic littermates. These results indicate that MMTV activates NK cells through superantigen-dependent and -independent pathways and supports the role of MMTV(C4) in the augmented NK activity observed in C4 HAN infiltrates. The progression of C4 HAN to tumor represents a model system for the analysis of how tumorigenesis may be affected by lesion-associated viruses.
Gill
R
R
Department of Immunology, Michigan Cancer Foundation, Detroit 48201.
Wang
H
H
Bluethmann
H
H
Iglesias
A
A
Wei
W Z
WZ
D000818:Animals; D001483:Base Sequence; D005260:Female; D006965:Hyperplasia / Q000382:microbiology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008212:Lymphocyte Depletion; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000382:microbiology; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011650:Pulmonary Alveoli / Q000382:microbiology / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000502:physiology*; D012192:Retroviridae Infections / Q000276:immunology / Q000382:microbiology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018089:Superantigens / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000382:microbiology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens