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Absence of Cell-Mediated Immunologic Tolerance to Leukemia Virus in Carrier Mice¹

From the Harvard Medical School, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Abstract

Several viruses have been reported to induce immunologic tolerance in mice when infection occurs in the prenatal or immediate postnatal period. Among these are lymphocytic choriomeningitis (LCM)³ virus (1–3) and murine leukemia viruses (MuLV) (4–6). Although Moloney murine leukemia virus (MuLV-M) can induce leukemia in both newborn and adult mice (7), there is a marked difference in host response in these two age groups. Inoculation into adults results in development of both humoral and cell-mediated immune responses to the virus, whereas in neonatally infected mice these responses appear to be either greatly reduced or undetectable (5, 8).

Recent results have cast doubt on the validity of the concept of immunologic tolerance to viruses. It now is generally accepted that humoral antibodies can be formed after neonatal infection with LCM virus (9), MuLV-M (10), Harvey murine sarcoma virus (MuSV-H) (10), and Gross murine leukemia virus (MuLV-G) (11, 12).

Footnotes

¹ These investigations were conducted under contract No. NIH-72-2012 within the Special Virus Cancer Program of the National Cancer Institute, National Institutes of Health, United States Public Health Service, and Grant 1 R01-CA12464-02, United States Public Health Service.

³ Abbreviations used in this paper: LCM, lymphocytic choriomeningitis; MuLV, murine leukemia viruses; MuLV-M, Moloney MuLV; MuSV-H, Harvey murine sarcoma virus; MuLV-G, Gross MuLV; PBS, phosphate-buffered saline; DTMK buffer, 0.002 M dithiothreitol, 0.04 M Tris HC1 at pH 7.8, 0.15 M MgAc₂, 0.06 M KC1; PFU, plaque-forming units; FBS, fetal bovine serum; complete MEMx4, 4-fold Eagle's minimal essential medium with amino acids, vitamins, FBS, penicillin, and streptomycin sulfate.

² M. R. Proffitt is a Postdoctoral Fellow of the Damon Runyon Memorial Fund.