Factors from lymphoid cell tumor affecting immune responses

Area of Science:

• Immunology
• Virology
• Oncology

Background:

• Friend leukemia virus (FLV) is known to induce erythroblastic leukemia in susceptible BALB/c mice.
• FLV infection leads to a significant depression of the humoral immune response to sheep red blood cells (SRBC).
• Both leukemogenesis and immunosuppression can be transmitted via cell-free viral homogenates from infected splenocytes.

Purpose of the Study:

• To investigate the nature of the immunosuppressive agent associated with Friend leukemia virus.
• To determine whether the virus itself or the leukemic cells are responsible for suppressing antibody formation.
• To assess the resistance of the immunosuppressive activity to physical and radiation inactivation.

Main Methods:

• Characterization of the immunosuppressive factor by heating, specific antisera, filtration, and ultracentrifugation.
• Assessment of resistance to irradiation by exposing leukemic cells and measuring their ability to induce leukemia and suppress immune responses.
• In vitro culture of normal spleen cells with normal or irradiated FLV-leukemic cells to evaluate antibody formation.

Main Results:

• The immunosuppressive activity was neutralized by heating and specific antisera, indicating a viral or proteinaceous nature.
• The suppressive factor passed through a 0.45 μm filter but not a 300,000 MW filter, consistent with a viral particle.
• FLV-leukemic cells and viral extracts remained highly resistant to inactivation by irradiation, with significant immunosuppressive activity persisting even after 32,000 rads.

Conclusions:

• The Friend leukemia virus (FLV) itself is directly responsible for the suppression of antibody formation.
• The immunosuppressive activity of FLV is remarkably resistant to high doses of irradiation.
• These findings highlight the potent and direct role of the virus in immune dysregulation during FLV infection.