Immunoregulatory circuits which modulate responsiveness to suppressor cell signals: characterization of an effector cell in the contrasuppressor circuit.
Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the ability to block the activity of suppressor T cells, a phenomenon that is referred to as contrasuppression. The effector cell which is derived from the interactions among the cells which comprise a contrasuppressor "circuit" is an Ly-1 T cell. It can be separated from Ly-1 helper cells by three criteria other than function: its generation is dependent on Ly-2+ cells, it is I-J+, and it sticks to the Vicia villosa lectin. Those cells which deliver help to B cells under the experimental conditions studied are not dependent on Ly-2+ cells for generation and neither express determinants that our anti-I-J antisera recognize nor stick to V. villosa. The mechanism by which these Ly-1 contrasuppressor cells function was elucidated by adding them to "'intermediate cultures" containing activated Ly-2 suppressor cells and in vivo immunized Ly-1.1-congenic helper cells. After 48 h in these intermediate cultures, the neonatal Ly-1.2 contrasuppressor cells and the Ly-2 suppressor cells were removed by treatment with the appropriate antiserum plus complement. The remaining activity of the in vivo generated Ly-1.1 helper cells was assayed in fresh cultures of B cells. The contrasuppressor cells not only diminished suppression of the Ly-1 helper cells by the Ly-2 suppressor cells in the intermediate culture, but actually conferred a state of relative resistance to suppression upon the helper cells. This state persisted after the contrasuppressor cells were removed. Why such a cellular circuit, which confers resistance to suppression, might be beneficial to neonatal mice and how considering its attributes might help explain some immunological paradoxes is the subject of discussion.
D000818:Animals; D000831:Animals, Newborn; D000950:Antigens, Ly / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D005802:Genes, MHC Class II; D007106:Immune Sera / Q000145:classification / Q000494:pharmacology; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D014176:Protein Biosynthesis; D011975:Receptors, Mitogen; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000950:Antigens, Ly; D007106:Immune Sera; D011975:Receptors, Mitogen