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Tolerance to viral antigens in Mov-13 mice carrying endogenized Moloney-murine leukemia virus
Abstract:
In virus-positive (V+) C57BL/6 Mov-13 mice, Moloney-murine leukemia virus (M-MuLV) is integrated into the germ line and expressed early in lymphoid and nonlymphoid organs. The pattern of immune reactivity to viral antigens in these mice was studied and compared to that of their virus-negative (V-) counterparts. Using a radioimmuno-binding or -precipitation assay, V- mice showed good antibody production after challenge with Moloney-murine sarcoma virus (M-MSV), but no antibodies were detected in V+ mice. Moreover, Mov-13 V+ mice failed to generate virus-specific cytotoxic T lymphocytes (CTL) in secondary mixed-leukocyte tumor cell culture (MLTC) while V- mice showed a strong cytotoxic response. This lack of activity in mass V+ cultures was due to a very low frequency of CTL precursors which did not increase following in vivo challenge with M-MSV or in vitro stimulation with MBL-2 Moloney leukemia cell line. These findings indicate that early M-MuLV activation in Mov-13 V+ mice induces a state of tolerance to viral antigens involving both the humoral and cellular immune responses and related to the high incidence of T-cell lymphomas.
Insights
Early Moloney-murine leukemia virus (M-MuLV) activation in virus-positive (V+) mice induces immune tolerance. This tolerance affects both antibody production and cytotoxic T lymphocyte responses, contributing to T-cell lymphomas.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Moloney-murine leukemia virus (M-MuLV) is integrated into the germ line of C57BL/6 Mov-13 mice.
- Viral antigens are expressed early in lymphoid and nonlymphoid organs of virus-positive (V+) mice.
Purpose of the Study:
- To investigate the immune reactivity to viral antigens in M-MuLV-infected mice.
- To compare immune responses in virus-positive (V+) and virus-negative (V-) Mov-13 mice.
Main Methods:
- Radioimmuno-binding and -precipitation assays were used to detect antibody production.
- Secondary mixed-leukocyte tumor cell culture (MLTC) was employed to assess cytotoxic T lymphocyte (CTL) responses.
- In vivo and in vitro stimulation assays were performed to evaluate CTL precursor frequency.
Main Results:
- Virus-negative (V-) mice produced antibodies after Moloney-murine sarcoma virus (M-MSV) challenge, while V+ mice did not.
- V+ mice failed to generate virus-specific CTLs in MLTC, unlike V- mice which showed a strong response.
- A very low frequency of CTL precursors in V+ mice did not increase upon M-MSV challenge or MBL-2 cell line stimulation.
Conclusions:
- Early M-MuLV activation in Mov-13 V+ mice induces immune tolerance to viral antigens.
- This tolerance encompasses both humoral and cellular immune responses.
- The observed immune tolerance is linked to the high incidence of T-cell lymphomas in these mice.