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Reversal of leukemia virus-induced immunosuppression in vitro by peritoneal macrophages
Abstract:
When spleen cells from mice infected with Rowson-Parr virus (RPV) were cultivated with sheep red blood cells (SRBC), antibody plaque responses were markedly lower than those in similarly cultivated spleen cells from normal mice. Addition of as few as 10(3) spleen cells from RPV-infected mice to cultures of normal aplenocytes markedly depressed the expected immune response. Although RPV-infected mice showed maximum immunodpression in vivo only during the first week after infection, their spleen cells, obtained later in the course of infection, depressed the immunologic responsiveness of normal splenocytes in vitro. Increased doses of SRBC or addition of bacterial lipopolysaccharide to cultures of spleen cells from immunodepressed, RPV-infected mice stimulated antibody formation, and near-normal numbers of antibody-producing cells were evident. Peritoneal exudate (PE) cells, but not thymus, bone marrow, or unfractioned spleen cells, restored immunocompetence to cultures of spleen cells from RPV-infected mice but did not affect the suppressive properties of the infected cells on normal splenocytes. The function of PE cell macrophages in restoring immunocompetence to infected spleen cells in cultures seemed related to a possible antigen-focusing activity of the cells; antibody-producing cell precursors in infected cultures seemed to be preferentially affected by the presence of normal PE cells.
Insights
Rowson-Parr virus (RPV) infection severely impairs mouse immune responses, reducing antibody production. However, peritoneal exudate cells can restore immunocompetence in infected spleen cells, suggesting a role for macrophages in immune restoration.
Area of Science:
- Immunology
- Virology
Background:
- Rowson-Parr virus (RPV) infection is known to cause immunosuppression in mice.
- The specific mechanisms by which RPV affects immune cell function are not fully understood.
Purpose of the Study:
- To investigate the impact of RPV infection on the immune response to sheep red blood cells (SRBC) in vitro.
- To identify factors that can restore immunocompetence in RPV-infected spleen cells.
Main Methods:
- Spleen cells from RPV-infected and normal mice were cultured with SRBC to assess antibody plaque-forming cell responses.
- RPV-infected spleen cells were co-cultured with normal aplenocytes to evaluate their suppressive effects.
- Various cell types (peritoneal exudate cells, thymus, bone marrow) were added to RPV-infected spleen cell cultures to assess restoration of immune function.
- Bacterial lipopolysaccharide was used as a stimulant in cultures.
Main Results:
- Spleen cells from RPV-infected mice showed significantly lower antibody plaque responses compared to normal mice.
- RPV-infected spleen cells suppressed the immune response of normal splenocytes in vitro.
- Increased SRBC doses or lipopolysaccharide stimulation partially restored antibody formation in infected cells.
- Peritoneal exudate (PE) cells, but not other tested cell types, restored immunocompetence to RPV-infected spleen cell cultures.
Conclusions:
- RPV infection profoundly suppresses B cell antibody production and immune responsiveness.
- Peritoneal exudate cells, particularly macrophages, play a crucial role in restoring immunocompetence to RPV-infected spleen cells, possibly through antigen focusing.
- The suppressive effects of RPV-infected cells on normal splenocytes were not overcome by PE cells, indicating distinct mechanisms of suppression and restoration.