Autoimmune response induction and regulation in rat erythrocyte-immunized mice

Area of Science:

• Immunology
• Autoimmunity
• Cellular immunology

Background:

• Antibody formation to self-red blood cells (RBC) is a complex process.
• Studies have investigated the relationship between antibody production to foreign and self-RBC.

Purpose of the Study:

• To investigate the mechanisms underlying antibody formation to self-RBC in immunized mice.
• To determine if autoimmune processes involve a breakdown of immunologic tolerance to self-RBC.
• To elucidate the role of splenocytes and antibodies in regulating immune responses to RBC.

Main Methods:

• Immunization of mice with rat RBC (rRBC).
• Assessment of antibody production to mouse RBC (mRBC) and rRBC.
• Splenocyte transfer experiments into irradiated and non-irradiated recipients.
• Treatment with cyclophosphamide (CP) and antibodies to I-J.
• Inoculation of antibodies to rRBC.

Main Results:

• Low-dose rRBC injections overcame low responsiveness to both mRBC and rRBC.
• rRBC-tolerant mice showed reduced anti-mRBC antibody production.
• Transfer of splenocytes from rRBC-immunized donors enhanced anti-mRBC and anti-rRBC antibody production in irradiated recipients.
• Splenocytes from rRBC-immunized donors inhibited anti-mRBC antibody production in non-irradiated recipients.
• This suppressive effect was abrogated by eliminating donor cells and could be mimicked by inoculating anti-rRBC antibodies.

Conclusions:

• Autoimmune processes against RBC are not associated with disordered immunologic tolerance to self-RBC.
• The immune response requires T-helper cells responding to foreign epitopes of RBC antigens.
• Splenocyte-mediated suppression of antibody production to self-RBC is regulated by feedback mechanisms involving antibodies to foreign RBC.