Generation and regulation of autocytotoxicity in mixed lymphocyte cultures: Evidence for active suppression of autocytotoxic cells Journal Article

   

Authors:	Rosenkrantz, K.; Dupont, B.; Flomenberg, N.
Article Title:	Generation and regulation of autocytotoxicity in mixed lymphocyte cultures: Evidence for active suppression of autocytotoxic cells
Abstract:	Using limiting dilution analysis, we have detected both the generation and suppression of autocytotoxic cells following autologous or allogeneic stimulation in vitro. Assay conditions were established in which the cytotoxic response toward an allogeneic sensitizing cell was consistent with a traditional single-hit kinetic model. Under identical conditions, cytolytic activity toward autologous phytohemagglutinin-activated lymphoblasts exhibited a distinct biphasic response. At low responder cell doses, a clear autocytotoxic response was observed. However, at higher responder cell numbers, this autocytotoxic reaction disappeared. This biphasic pattern of autocytotoxicity developed after stimulation with allogeneic or autologous peripheral blood mononuclear leukocytes (PBL) or Epstein-Barr virus-transformed B cells. This pattern of response is consistent with the counterprised actions of two distinct cell population, an autoaggressive population and a lower frequency autosuppressor population. Autocytotoxicity was not the result of mitogenic or xenogeneic antigenic stimulation, as it was observed after stimulation with autologous PBL in autologous serum and an autologous interleukin 2 preparation. Thus, cells capable of autocytotoxicity are present in peripheral blood but at a lower frequency than allocytotoxic T lymphocytes. Furthermore, autoaggressive cells are down-regulated by an autologous suppressor population. These findings suggest that immunologic self-tolerance is, at least in part, an actively maintained condition. Disturbances in this autoregulatory network may have relevance to the pathogenesis of some autoimmune diseases and graft-versus-host disease.
Keywords:	human cell; immunosuppressive treatment; human herpesvirus 4; lymphocyte culture; human; priority journal; autocytotoxicity
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	82
Issue:	13
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	1985-07-01
Start Page:	4508
End Page:	4512
Language:	English
DOI:	10.1073/pnas.82.13.4508
PROVIDER:	scopus
PMCID:	PMC391131
PUBMED:	2989827
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0021955724&doi=10.1073%2fpnas.82.13.4508&partnerID=40&md5=7aaf6dcb9506e4b3f672792f811d502d
Notes:	Article -- Export Date: 26 October 2021 -- Source: Scopus

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