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H-2-determined kinetic differences for the induction of nucleoside-specific suppression
Abstract:
The kinetic and the H-2 requirements for the induction of nucleoside-specific suppression were examined in several strains of mice; specifically, whether adenosine (A)-coupled spleen cells given intravenously suppress the primary response to adenosine-KLH. The adenosine system was chosen because C57Bl/6 mice were originally found to be resistant to immune suppression when challenged 5 days after treatment with adenosine-coupled spleen cells. (Raps et al. J. Immunol. 126, 1542, 1981.) It was determined (i) whether A-specific nonresponsiveness is inducible in strains other than C57Bl/6; (ii) whether changes in hapten density on the A-conjugated spleen cells could alter C57Bl/6s ability to become nonresponsive, and (iii) whether there are interstrain differences in the time required to induce A-specific suppressor T cells (Ts). The results show that there are H-2-associated differences in the time required to induce A-specific immune suppression. While A-spleen cells failed to suppress the A-specific response in C67Bl/10 (H-2b), they did induce unresponsiveness in B10.D2 (H-2d on C57Bl/10 background). A 2.5-fold increase in epitope density of adenosine on cells did not influence the kinetics of suppression. C67Bl/6 were resistant to suppression on Day 5, but like the CB6F1, susceptible to unresponsiveness 10 days after treatment. Nonresponsiveness was T-cell-mediated and transferable across IgH-V barriers. Suppression induced by Balb/c donor mice is transferable to Igh-incompatible CAL-20 mice. These results are discussed in the context of genetic restrictions which regulate suppressor T-cell interactions.
Insights
Mice strains show genetic differences in developing adenosine-specific immune suppression, influenced by H-2 genes. This T-cell-mediated suppression is transferable, highlighting genetic restrictions in immune regulation.
Area of Science:
- Immunology
- Immunogenetics
Background:
- Adenosine-specific immune suppression was previously studied in C57Bl/6 mice, which showed resistance to suppression by adenosine-coupled spleen cells.
- Investigating immune suppression kinetics and H-2 requirements is crucial for understanding immune regulation.
Purpose of the Study:
- To determine if adenosine-specific nonresponsiveness is inducible in mouse strains beyond C57Bl/6.
- To assess the impact of hapten density on adenosine-conjugated cells on immune nonresponsiveness.
- To identify interstrain variations in the induction time for adenosine-specific suppressor T cells (Ts).
Main Methods:
- Administered intravenous adenosine-coupled spleen cells to various mouse strains.
- Assessed the primary immune response to adenosine-keyhole limpet hemocyanin (KLH).
- Analyzed T-cell-mediated suppression and its transferability across immunoglobulin heavy chain variable (IgH-V) barriers.
Main Results:
- H-2 haplotype differences were observed in the kinetics of adenosine-specific immune suppression induction.
- C57Bl/10 (H-2b) mice were resistant to suppression, while B10.D2 (H-2d) mice became unresponsive.
- C57Bl/6 mice, initially resistant on Day 5, became susceptible to unresponsiveness by Day 10, similar to CB6F1 mice.
Conclusions:
- Genetic factors, specifically H-2 associations, significantly influence the induction of adenosine-specific immune suppression.
- Adenosine-specific immune nonresponsiveness is mediated by T cells and can be transferred, indicating complex genetic regulation.
- These findings provide insights into the genetic restrictions governing suppressor T-cell interactions in adaptive immunity.