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Biomedical subjects

W S Lapp

Publications and source records attributed to W S Lapp.

At least 55 records · Page 3Linked to original sources

Precocious thymic involution manifest by epithelial injury in the acquired immune deficiency syndrome.

Thymuses from six heterosexual Haitian patients with the acquired immune deficiency syndrome (AIDS) were studied by light microscopy and the findings were compared with those from three control groups. The control groups included 1) five age-matched Haitian hospital patients; 2) ten age- and sex-matched Montreal patients who had died suddenly or had had brief illnesses; and 3) 20 middle-elderly Montreal patients who had experienced chronic, wasting illnesses or prolonged hospitalization. Thymuses from patients with AIDS demonstrated pronounced involution, effacement of the cortex and medulla, marked thymocyte depletion, variable degrees of plasma cell infiltration and fibrosis, and, above all, absence of Hassall's corpuscles. Thymuses from Haitian and Montreal control subjects who had died suddenly or had brief illnesses demonstrated minimal involution and abundant Hassall's corpuscles. Although thymuses from 12 of the chronically ill control subjects demonstrated marked involution, architectural effacement, and absence of Hassall's corpuscles, partial architectural preservation and variable numbers of Hassall's corpuscles were observed in eight of these subjects. Thus, the extent of thymic involution observed in patients with AIDS antedates that incurred with aging and supersedes that induced by sustained stress and inanition. The loss of Hassall's corpuscles in patients with AIDS suggests that the thymic epithelium either incurs a form of injury or undergoes precocious involution during the illness. Whether this lesion is central to the pathogenesis of AIDS or merely a reflection of intense, sustained stress coupled with accelerated physiologic involution is unknown. It is possible that the disappearance of Hassall's corpuscles may indicate important, although as yet cryptic events within the thymic microenvironment in this syndrome.

Acquired Immunodeficiency Syndrome↗

The graft-versus-host reaction and immune function. I. T helper cell immunodeficiency associated with graft-versus-host-induced thymic epithelial cell damage.

The injection of parental A strain lymphoid cells into adrenalectomized CBAxA F1 (BAF1) mice induced a chronic graft-versus-host (GVH) reaction resulting in T cell and B cell immunosuppression as well as thymic epithelial cell injury, but not stress-related thymic involution. Thymocytes from BAF1 mice undergoing a GVH reaction were studied for their ability to reconstitute T helper cell (TH) function and phytohemagglutinin (PHA) and concanavalin A (Con A) mitogen responses in thymectomized, irradiated, BAF1 mice reconstituted with normal syngeneic bone marrow (ATxBM). Thymocytes from BAF1 mice early after the induction of a GVH reaction (days 10-12) were as effective as normal thymocytes in reconstituting TH and mitogen responses. Thymocytes from BAF1 mice 40 or more days after the induction of a GVH reaction did not reconstitute either the TH function or PHA and Con A responses in ATxBM mice. The inability to reconstitute ATxBM mice was not due to the presence of suppressor cells contained in the thymocyte inoculum. It is proposed that GVH-induced thymic epithelial cell injury blocks or arrests normal T cell differentiation, resulting in a population of thymocytes that lack the potential to become competent T helper cells or mitogen-responsive cells when transferred into ATxBM mice. This thymic functional defect results in a permanent TH immunodeficiency in mice experiencing a chronic GVH reaction.

Adrenalectomy↗

Macrophage activity in mice undergoing chronic graft-versus-host reactions.

The functional state of the mononuclear phagocyte system has been investigated in mice undergoing chronic graft-versus-host (GVH) reactions (GVHR), initiated by the injection of parental DBA/2 lymphoid cells into (DBA/2 X C57BL/6)F1 hybrid mice. Macrophage function was assessed in vivo by the ability to develop host resistance to infection with Listeria monocytogenes and found to be normal in GVH mice, as measured by the development of resistance during the early phase of natural (macrophage-mediated) resistance to the infection. During the later phase of acquired immunity to listerial infection, GVH mice had lowered resistance, but this was attributed to impaired T cell immunity rather than to defective macrophage function. The inflammatory response to a phlogistic agent, thioglycolate, was also found to be normal in GVH mice, as measured by the accumulation of inflammatory macrophages in the peritoneal cavity. In an in vitro assessment of macrophage function, phagocytosis was found to be enhanced initially (2 weeks following GVHR induction) but it subsequently became depressed for the duration of the study (12 weeks after GVHR induction). Macrophage chemotactic activity was initially normal, then became depressed and remained so for the duration of the study. Thus, despite the profound suppression of specific immunity induced by the GVH reaction and the functional defects of GVH macrophages apparent in vitro, the response of the mononuclear phagocyte system to in vivo stimuli, such as infection or inflammation, is unimpaired in GVH mice.

Animals↗

The graft-versus-host reaction and immune function. II. Recruitment of pre-T-cells in vivo by graft-versus-host-induced dysplastic thymuses following irradiation and bone marrow treatment.

The graft-versus-host (GVH) reaction induces thymic dysplasia and an arrest in T cell differentiation. Studies were performed to test the effect of irradiation and reconstitution with bone marrow on GVH-induced thymic dysplasia and T cell differentiation. GVH reactions were induced in CBAxAF1 adult mice by the injection of A strain lymphoid cells. All GVH-reactive mice were immunosuppressed by day 7 after GVH induction and thymic dysplasia was evident by day 24. Forty days after the induction of the GVH reaction the mice were irradiated (850 rads) and repopulated with 10-15 X 10(6) syngeneic or parental bone marrow cells. Thirty days after irradiation and bone marrow reconstitution, GVH-reactive mice were used for histological and functional studies. These mice displayed near-normal thymus morphology with scattered epithelial cells in the medulla, and normal numbers of Thy-1-positive cells. Donor cells had totally repopulated thymuses of irradiated bone marrow reconstituted mice by day 19 after irradiation. T helper cell function did not recover in the reconstituted mice. These results suggest that (1) the process responsible for GVH-induced thymic dysplasia is radiosensitive, and (2) the thymus has the potential to regenerate a normal structure, but fails to regain normal function.

Animals↗

Mammary carcinoma arising in mice undergoing a chronic graft-versus-host reaction.

A graft-versus-host reaction (GVHR) was induced in 30 (CBA X A)F1 mice by the iv injection of 50 X 10(6) parental strain A lymphoid cells. Solid tumors emerged in 5 of 10 experimental animals that survived beyond 14 months after the GVHR was initiated. The neoplasms were judged to be mammary carcinomas by light and electron microscopic examinations. C-type RNA viral structures were observed in some tumor cells. The neoplasms were successfully transplanted into syngeneic animals by either sc or ip injections of tumor cell suspensions. Tumor transfer to syngeneic mice was not possible if only spleen cells from tumor-bearing animals were transferred. No tumors developed in an age-matched control group that received no treatment.

Animals↗

T cell functional defect associated with thymid epithelial cell injury induced by a graft-versus-host reaction.

The injection of parental strain cells into adrenalectomized (CBA x A)F1 mice induced a graft-versus-host (GVH) reaction which was morphologically characterized by thymus epithelial cell injury but not stress-related thymic involution. Thymocytes from mice undergoing a GVH reaction were studied for their ability to reconstitute allograft reactivity in thymectomized, irradiated, bone marrow reconstituted (ATxBM) (CBA x A)F1 mice. Thymocytes of mice experiencing a GVH reaction were theta-positive during the course of the reaction, however, by 40 days after GVH induction these thymocytes were unable to reconstitute allograft reactivity to H-2-incompatible skin grafts. It is proposed that GVH-induced thymic epithelial cell injury prevents or arrests normal T cell differentiation, resulting in a population of thymocytes which lack complete functional capability.

Animals↗

Evidence for two types of non-specific suppressor cells activated by the graft-versus-host reaction in mice.

In vitro experiments were carried out to investigate the immunosuppressive efect of different populations of spleen cells obtained from animal experiencing a graft-versus-host reaction (GVHR). To induce the GVHR, parental lymphoid cells were injected into adult F1 hybrid mice. GVHR-activated spleen cells (GVH-sc) taken at different times post-GVHR induction were separated into adherent and non-adherent fractions and treated with anti-theta serum plus complement. The different types of GVH-SC were added to either parental (donor-type) of F1 (host-type) normal spleen cells and cultured with sheep erythrocytes in a modified Marbrook chamber. It was found that both adherent and non-adherent 10-day GVH-SC significantly inhibited the plaque-forming cell response of F1 normal spleen cells but not that of parental normal spleen cells. Significant suppression of the parental response was observed following the addition of 15-day GVH-SC or anti-theta treated adherent and non-adherent 7-day GVH-SC. The results suggest that the non-specific immunosuppressive effect of GVH-SC is mediated by GVHR-activated macrophages and B lymphocytes found in the anti-theta treated adherent and non-adherent fractions of the GVH-SC suspensions respectively.

Animals↗