A cellular basis for genetically controlled immunologic unresponsiveness in mice: tolerance induction in T-cells

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• H-2(q) mice (DBA/1) are non-responders to the synthetic amino acid polymer (Glu, Ala, Tyr(10)).
• Other mouse strains with different H-2 alleles effectively produce antibody responses to this polymer.

Purpose of the Study:

• To investigate the immunological basis for H-2(q) mice's non-responsiveness to (Glu, Ala, Tyr(10)).
• To explore the role of T-cells (thymus-processed lymphocytes) in this immune tolerance.

Main Methods:

• Immunization of H-2(q) mice with (Glu, Ala, Tyr(10)) polymer.
• Assessment of antibody production and thymocyte DNA synthesis in response to the antigen.
• Analysis of immune memory after secondary immunization.
• Evaluation of antibody response when the polymer is complexed with a carrier, and the effect of prior free polymer exposure.

Main Results:

• H-2(q) mice thymocytes recognize the antigen, indicated by DNA synthesis, but do not develop immunological memory.
• Non-responder mice can produce antibodies when the polymer is presented with an immunogenic carrier.
• Pre-exposure to the free polymer can transiently suppress antibody formation even when complexed with a carrier.

Conclusions:

• The unresponsiveness in H-2(q) mice is attributed to their T-cells' heightened tendency to induce or develop immunological tolerance.
• This suggests a specific T-cell mediated tolerance mechanism in H-2(q) mice against this synthetic polymer.