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J F Albright

Publications and source records attributed to J F Albright.

54 records · Page 3Linked to original sources
PubMed1981

Inhibition of murine humoral immune responses by substances derived from trypanosomes.

Previous studies of depressed immune responses in mice infected with the mouse-specific Trypanosoma musculi have produced no evidence of major involvement of typical suppressor lymphocytes or macrophages. We continue this line of investigation in the present report by demonstrating that: a) T. musculi strongly suppress the responses of nude mouse spleen cells to the T-independent antigen, TNP-LPS; b) spleen cell preparations of infected mice display a substantial proportion of cells bearing trypanosome-derived substances (TDS) demonstrable by specific rabbit antibody against T. musculi (RATS); c) treatment of spleen cells from infected mice with RATS plus C eliminates the inhibitory effect of these spleen cells on the immune responses of co-cultivated normal spleen cells; d) incubation in vitro of normal spleen cells with an extract of T. musculi results in progressive loss of the cells to respond to antigens and, in addition, confers on the treated cells to respond to antigens and, in addition, confers on the treated cells the property of inhibiting the responses of co-cultivated normal spleen cells; e) T. lewisi, the rat-specific trypanosome, fails to inhibit murine immune responses. We conclude that the immunoinhibitory effects of T. musculi on murine immune responses are associated with the cytophilic binding of TDS (possibly in the form of immune complexes) and that this vigorous mechanism of inhibition will be shown to involve nonspecific mitogenic and/or biosynthetic activation of lymphocytes.

Animals↗
PubMed1978

Mechanisms of trypanosome-mediated suppression of humoral immunity in mice.

Spleen cells from Trypanosoma musculi-infected mice were unable to respond to sheep erythrocyte antigen in vitro; moreover, they suppressed the responses of normal spleen cell cultures in dose-dependent fashion. Suppression was maximal with spleen cells obtained during maximal parasitemia and waned as the donors recovered from infection. A macrophage-enriched population of spleen cells from infected mice, prepared either by adherence to plastic or by density gradient centrifugation, was not contaminated by the parasites and was not suppressive, whereas the plastic-nonadherent population was both contaminated and suppressive. Adherent and nonadherent cells of infected mice, separated by use of nylon wool columns, were almost equally suppressive and equally contaminated by trypanosomes. Addition of specific rabbit antiserum against T. musculi to cultures containing cells from infected mice eliminated contaminating parasites and alleviated suppression exerted by cells obtained from mice early during the course of infection but not after 12-15 days of infection. The suppression exerted by enriched T-cells obtained from mice on day 12 of infection was largely alleviated by use of the antiserum. A large portion of cells obtained on day 14 of infection could be killed by the antiserum and complement. It appeared that soluble substances derived from the parasites acted directly on B lymphocytes or essential assistant cells rather than by activating suppressor T cells or macrophages.

Animals↗
PubMed1978

Immunosuppressive activity associated with a reticulum cell sarcoma of aged mice.

Aging BC3F1 hybrid mice frequently develop a reticulum cell sarcoma (RCS) causing marked hypercellularity of lymphoid tissues and pronounced suppression of humoral immunity. Cells of malignant spleens gave feeble responses in vitro to thymus-dependent and -independent antigens; moreover, they suppressed normal spleen cell responses to the antigens. The RCS was passed, serially, in young mice and the spleen and ascites cells of these recipients suppressed normal cell responses in vitro. Malignancy resulted in a substantial increase in the proportion of spleen cells of relatively lower density as determined by BSA gradient centrifugation; the cells of lower density were strongly immunosuppressive. The suppressive cells appeared to be neither typical T cells nor macrophages. Humoral suppressive substances associated with the RCS were demonstrated in vivo. The suppressive influence of the RCS may account for the hostile milieu in old BC3F1 mice with respect to lymphohematopoietic cells.

Age Factors↗
PubMed1978

Growth of Trypanosoma musculi in cultures of murine spleen cells and analysis of the requirement for supportive spleen cells.

Growth of Trypanosoma musculi in vitro has been achieved. The number of parasites increased by more than 1,500-fold in less than 8 days under the most suitable conditions. The rate and magnitude of growth was comparable to that which occurs in inoculated murine hosts. Maximum growth was displayed in cultures composed of RPMI 1640 medium supplemented with fetal calf serum, murine spleen cells, and foreign erythrocytes (sheep). No growth occurred in the absence of spleen cells. The adherent, macrophage-rich population supported parasite growth much better than did the nonadherent population. Parasite growth was excellent in the presence of irradiated spleen cells or of cells from thymectomized, irradiated, bone marrow-reconstituted mice. The important cells appeared to be macrophages. The beneficial effect of sheep erythrocytes probably resulted from preoccupation or stimulation of phagocytes. Soluble substances released by spleen cell cultures promote parasite growth, as was shown by experiments with double-compartment culture vessels. The utility of this culture system for analysis of host immune responses against the trypanosome was demonstrated.

Animals↗
PubMed1970

Antigen competition: antigens compete for a cell occurring with limited frequency.

Experimentally altered ability of transferred spleen cells to generate hemolytic plaque-forming cells provided evidence that antigens compete for a type of multipotential cell that contributes to the formation of immunologically competent units. De'ay of exposure of transferred spleen cells to antigen provided results which suggest that different types of cells interact to form competent, antigen-reactive units even in the absence of antigen.

Animals↗
PubMedDate not supplied

Impaired natural killer cell function as a consequence of aging.

Alex Comfort wrote (1979): "... nobody needs long-lived mice." His point was, of course, that as much as possible, research should be done with humans "... who are the beneficiaries in mind ..." In this paper we hope to show that long-lived mice have been useful, if not essential, for conducting studies on the aging of innate immunity, specifically the NK cell component of the system. NK cells are activated early in the course of Trypanosoma musculi infections, which we employ as a model. We have generated evidence that the relatively severe infections of aged mice with T. musculi, are attributable, in part, to (a) functionally defective NK cells, the defect(s) being retained by LAK cells that arise from them, and (b) deficient amounts of IL-2 required to convert NK to LAK cells. Defective macrophages, which are the effector cells responsible for eliminating T. musculi, may also accumulate in aged animals. We postulate that the functionally deficient NK cells fail to generate adequate amounts of IFN gamma (and perhaps, TNF alpha) to optimally activate macrophages. This inadequacy can explain the weak ability of aged mice to control the early stage of T. musculi infection preceding the appearance of the more slowly-developing acquired immune response.

Aging↗