Biomedical subjects
Publications and source records attributed to A C Corsini.
Delayed type hypersensitivity reactions in mice sensitized to dinitrofluorobenzene were assessed by measuring the increase in weight of the ears challenged with antigen. The method has proved reliable for assessment of DTH reactions when results are expressed as weight ratios between challenged and unchallenged ears.
T. brucei infection in mice causes generalized immunosuppression with multiple changes in the cells of the lymphoid tissue. Loss of B cell responsiveness to antigens and mitogens, and the induction of suppressive T-cells and macrophages, have been previously reported (Hudson, Byner, Freeman & Terry, 1976; Corsini, Clayton, Askonas & Ogilvie, 1977; Jayawardena & Waksman, 1977). In this study, purified B- or T-cell populations from infected mice have been tested functionally in vitro or in vivo by transfer into syngeneic irradiated hosts to separate the cells from trypanosomes or their products. B-memory cells for thymus dependent (DNP-KLH) and thymus independent (DNP-Ficoll) antigens are depleted or lose their potential to respond to the antigen during T. brucei infection. Similarly, purified T-helper cells, and T-cells reactive to allogeneic target cells in mixed lymphocyte reactions are functionally defective. By 16 days of infection all these responses are less than 10% of the normal level. The loss of B-cell function follows the peak parasitaemia and is accompanied by increases in the serum levels of both IgM and IgG. Enhanced Ig production and decline in B-cell potential also occur in T-deprived mice and in CBA/N mice which lack a subset of T-independent B-cells. Cells affecting delayed hypersensitivity reactions retain their activity throughout trypanosome infection and so far provide the only exception to the general decline in immune potential.
The functional changes in splenic lymphoid populations from mice infected with T. brucei strain S42 were studied throughout the 3 weeks of infection. Within a week of infection, proliferation of B and T cells profoundly increased as shown by 3H-labelled thymidine incorporation and fluorescent staining of surface Ig; the spleen cells secreted high levels of both IgM and IgG immediately cells were put into culture; but with progressing infection this Ig production declined. The early effect on T cells was reflected by lack of responsiveness to PHA. B-cell potential was studied in low-density cultures treated with lipopolysaccharide (E. coli). Normal spleen cells proliferate extensively in these cultures with subsequent secretion of IgG as well as IgM. The ability to proliferate and produce Ig in response to LPS was severely depressed by day 7 and almost totally absent by day 12 of infection. Removal of T cells from the spleen cells obtained early in infection partly restored the response to LPS but as the infection neared its fatal end, B-cell potential appeared to become exhausted. Macrophages obtained from infected mice even early in infection profoundly depressed the ability of normal spleen cells to proliferate and secrete immunoglobulin in LPS cultures. The general immunodepressing effect of trypanosomes can be attributed to clonal exhaustion of B-cell potential caused by an undefined blastogenic stimulus from the parasites which may operate at least in part by the generation of suppressive T cells and macrophages.