Suppression of in vitro CML generation by alloactivated lymphocytes: analysis of antigen-nonspecific suppressive mechanisms.
We have investigated the in vitro phenomena associated with antigen-nonspecific suppression of mixed lymphocyte culture (MLC) responses by allocativated lymphocytes. Using an experimental system that we described in a previous communication, we observed that a) the degree of suppressive activity generated by allocativation correlates directly with the intensity of proliferation observed during induction of suppressive activity, b) suppressive activity segregates exclusively with proliferating (lymphoblast) subpopulations of alloactivated lymphocytes, c) when suppressive cells are included in MLC, subsequent [3H]thymidine incorporation is enhanced and accelerated, rather than impaired, and d) a considerable proportion of the cells recovered from suppressed MLC appear to be the progeny of the suppressive population, and not the progeny of the MLC responder population. These data suggest that antigen-nonspecific suppression mediated by alloactivated lymphocytes has two related components: 1) cytokine preemption by suppressive (alloactivated) lymphocytes, and 2) MLC responder cell dilution by the progeny of suppressive lymphocytes. These data are consistent with the hypothesis that the antigen-nonspecific suppressive activity of alloactivated lymphocytes can reflect the coincidental ability of activated T cells to recognize and respond to mitogenic lymphokines in vitro. The data further explain why antigen-nonspecific suppression is difficult to reverse by addition of exogenous lymphokines to suppressed MLC.
Orosz
C G
CG
Ferguson
R M
RM
D000818:Animals; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D004261:DNA Replication; D005260:Female; D007165:Immunosuppression Therapy; D007700:Kinetics; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*