Cell interactions that regulate the T-cell dose-response profile to concanavalin A.
We have tested the ability of structures on macrophage (M phi) membranes (M phi-MEM) and on several other types of cells with Fc receptors to affect the DNA synthetic response of concanavalin-A-stimulated T cells. Of the cells tested, only M phi-MEM have the capacity to relieve the suppression produced by supra-optimal doses of the mitogen. The M phi-MEM do not increase Con A responses by altering the stimulatory capacity of the Con A. These observations, analysed together with previous results, which have indicated that live intact M phi are required for the transfer of information between lymphocyte sets and that M phi-MEM preparations can act as competitive antagonists for this function, are interpreted as follows: some supraoptimal doses of Con A activate suppressor cells, which are responsible for limiting the DNA synthetic response to the mitogen; the M phi-MEM abrogate this suppression by absorbing the signal that activates the suppressor cell. Kinetic studies suggest that the M phi-MEM do not affect the activity of already activated suppressor cells. We also found that Con A usually activates two separately responding T-cell populations with different sensitivities to dose and to time of contact with mitogen and that the suppression of both populations can be relieved by M phi-MEM. These results support the notion that the overall immunological circuit is composed of multiple independently regulated mini-circuits, with M phi acting as transmission posts for intra- and perhaps also inter-circuit communication.
Naidorf
K F
KF
Laboratory of Cellular Immunology, Howard Hughes Medical Institute, New Haven, Connecticut, USA.
Ptak
W
W
Gershon
R K
RK
D000818:Animals; D002450:Cell Communication; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
D003208:Concanavalin A