Regulatory cellular interactions in the primary mixed lymphocyte reaction.
Limiting dilution analysis (LDA) of allogeneic and syngeneic murine mixed lymphocyte reactions was used to study the heterogeneity both of the responding spleen cells and of the stimulating antigen-presenting dendritic cells (DC). In contrast with traditional LDA of single-hit processes, a non-linear dependence of the proportion of negative microcultures on responding spleen cell concentration was obtained. The non-linearity of this LDA plot was interpreted as being the result of a competitive interaction between two types of limiting precursor cells. The regulatory and stimulatory functions of DC were investigated in the same LDA systems by testing various levels of DC from spleen or thymus as limiting cells in the presence of a constant quantity of syngeneic splenic responder T cells. This revealed a functional heterogeneity amongst DC, which were found to suppress proliferation of responder cells at low DC levels but to stimulate proliferation at higher levels. At levels where splenic DC became stimulatory, thymic DC remained suppressive.
Dozmorov
I
I
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
Kalinichenko
V
V
Süss
G
G
Shortman
K
K
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology