Biomedical subjects

S Macrae

Publications and source records attributed to S Macrae.

5 recordsLinked to original sources

PubMed1979

Effect of gold sodium thiomalate on murine lymphocyte functions.

The in vitro effects of gold sodium thiomalate (GTM) on various murine splenic lymphocytic functions were tested. The presence of GTM in cultures of splenic cells suppressed anti-hapten responses to both thymus-independent and thymus-dependent antigens. GTM also suppressed the in vitro generation of cytotoxic effector cells as well as the mitogenic response to both T cell and B cell mitogens. This suppression could not be reversed by the addition of irradiated spleen cells. Spleen cells exposed to GTM for 4 hr prior to culture also exhibited similarly suppressed functions, although their functional capacity could be fully restored by the addition of irradiated spleen cells. These results show that GTM inhibits both humoral and cellular immune mechanisms and appears to act primarily at the accessory (macrophage) cell level, with perhaps a secondary effect on T lymphocytes.

Animals↗

PubMed1979

Differentiation of functionally active mouse T lymphocytes from functionally inactive bone marrow precursors. III. Induction of T-cell activities by growth of bone marrow on feeder layers prepared from mouse thymocytes.

The ability of small and large T precursor cell pools to differentiate into mature functional T lymphocytes on thymus feeder cell layers or in the presence of a supernatant prepared from such feeder layers was compared. Evidence was obtained showing that the small cell pool differentiated as effectively in the presence of soluble factors prepared from the thymus cultures as in the presence of the thymus cells themselves. In contrast, large stem cells apparently needed cellular contact with the thymus feeder cultures in order to promote differentiation, though a time point could be found at which further differentiation from this precursor pool would also occur in the presence of the thymus culture supernatant only. These data concurred with evidence from in vivo experiments for two pools of T-cell precursors which differentiated in thymectomized or thymus-intact recipients respectively.

Animals↗

PubMed1979

Differentiation of functionally active mouse T lymphocytes from functionally inactive bone marrow precursors. IV. Recovery of T-cell function from bone marrow precursors in a histo-incompatible environment.

Regeneration of T-cell activities in vivo or in vitro from mouse bone marrow precursors differentiating in the presence of an allogeneic thymus was investigated. The data indicated that T-depleted bone marrow cells fail to affect long-term reconstitution of allogeneic recipients unless a pool of rapidly maturing T-precursor cells is also removed (post-thymic pool). Animals reconstituted with pre-thymic bone marrow stem cells become stable chimaeras in which cells capable of generating an in vitro CML response to host antigens, as well as cells capable of suppressing that response, could be demonstrated. Similar data (CML directed against the H-2 antigens of the 'host' thymus feeder layer and cells capable of inhibiting that response) were obtained when pre-thymic bone marrow cells were grown in vitro on allogeneic thymus feeder cells. When cytotoxic T-lymphocyte precursor (CTLp) and helper (CTLh) cells were separately investigated, a restriction in their co-operation for an anti-host response was observed when precursor cells differentiated in an allogeneic environment. Only CTLp and CTLh differentiating in the presence of the same allogeneic thymus source (whether in vivo or in vitro) could co-operate to generate CTL directed to H-2 antigens of that thymus source.

Animals↗

PubMed1979

MHC restriction of murine T lymphocyte reactivity analysed by growth of bone marrow cells in vitro on thymus epithelial monolayers.

Mature mouse T lymphocytes, derived from long-term culture of bone marrow cells on thymus epithelial monolayers, were analysed with respect to their ability to co-operate with B cells (for antibody production) or T cells (in the generation of cytotoxic cells) when the bone marrow T precursor cells and the thymus epithelial cells differ at defined regions of the major histocompatibility complex. A pool of more mature bone marrow T-cell precursors gave rise to T cells interacting only with T/B lymphocytes sharing MHC determinants with the strain of origin of the bone marrow cells used. In contrast, a more immature bone marrow T-cell precursor pool produced T lymphocytes which had acquired MHC restriction (in terms of co-operativity with T/B cells) as defined by the MHC determinants of the thymus epithelium, and not those MHC determinants of the cultured bone marrow population. In addition, some evidence was obtained for Ir gene control (mapping in the MHC region) in the development of the repertoire of T cells involved in production of cytotoxic responses in vitro to TNP-modified self antigens.

Animals↗

PubMed1978

Analysis of mechanisms of maintenance of neonatally induced tolerance to foreign alloantigens.

Mice made tolerant to allogeneic tissues in neonatal life have been examined at different times for their ability to respond to the tolerizing determinants in a variety of assays (in vitro CML, MCL and in vivo GvH assays). All animals were tolerant in terms of their inability to produce CTL to the relevant determinants, and to induce GvH in lethally irradiated F1 recipients. Nevertheless, some mice also showed a normal MLC proliferative response and contained antigen-specific serum inhibitory factors, while other mice contained apparently antigen-specific suppressor cells. The pool of the latter, futhermore, was expanded considerably upon adoptive transfer of tolerant cells (with tolerizing antigens) to lethally irradiated syngeneic recipients. The data are compatible with the notion that suppression of clonal expansion represents the primary mechanism of tolerance maintenance (induction), and that the infrequently observed serum reactivity in such tolerant mice represents a vestige of the means whereby-cell mediated suppression was induced.

Animals↗