Date of Award


Degree Type


Degree Name

Doctor of Philosophy


This thesis defines distinct immunoregulatory mechanisms which naturally exist in murine bone marrow (BM). Physical separation of BM cells revealed two immunoregulatory cell populations: a suppressor activity present in a fraction of large, low density BM cells predominantly of myeloid and blast cell morphology; and an enhancing activity contained in a fraction of small, high density BM cells enriched for lymphocytes. Both activities are associated with the production of soluble mediators which possess analogous function to the immunoregulatory cells.;The population of cells responsible for immune suppression have been referred to as Natural Suppressor (NS) cells. NS cells are unique in that they are not antigen- or MHC-restricted, and do not require specific priming to function. They suppress a variety of immune responses, including antibody (Ab), mitogen, and mixed lymphocyte reaction (MLR) responses. NS cells were routinely found in the BM of normal as well as severe combined immune-deficient (SCID) mice, and expressed no surface markers characteristic of B, T, M{dollar}\emptyset{dollar}, and NK/LAK cells. The culture of BM cells in IL-2 containing supernatants resulted in the generation of cells possessing potent NS as well as Natural Killer (NK) activity, suggesting that both NS and NK may be associated with a common family of cells.;Bone marrow cells secrete two soluble mediators which act in an analogous fashion to the suppressive and enhancing activities present in murine BM. These are bone marrow derived suppressor factor (BDSF) and bone marrow derived enhancing factor (BDEF). BDSF is contained in a low MW (1-10 kDa) fraction of BM culture supernatant which suppresses Ab and MLR, but not mitogen-driven responses. BDSF prevents production of IL-2 in the MLR, and BDSF-suppressed MLR responses can be reconstituted by the addition of exogenous IL-2. Therefore it is proposed that absence of IL-2 production due to BDSF results in clonal anergy or non-responsiveness.;BDEF ({dollar}>{dollar} 10 kDa) augments Ab and MLR responses, but cannot synergize with mitogen to induce proliferation. BDEF is directly mitogenic for murine thymocytes, specifically those which do not express the receptor for the lectin peanut agglutinin (PNA{dollar}\sp-{dollar}) and most resemble mature T-cells. The ability of BDEF to induce T-cell proliferation may be intimately associated with augmentation of both humoral and cellular responses.



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