Peripheral Lymphoid System Research Articles

Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues.

During early fetal development, T cell precursors home from fetal yolk sac and liver to the epithelial thymic rudiment. From cells that initially colonize the thymus arise mature T cells that populate T cell zones of the peripheral lymphoid system. Whereas colonization of the thymus occurs late in the final third of gestation in the mouse, in birds and humans the thymus is colonized by hematopoietic stem cell precursors during the first third of gestation. Using a large series of early human fetal tissues and a panel of monoclonal antibodies that includes markers of early T cells (CD7, CD45), we have studied the immunohistologic location and differentiation capacity of CD45+, CD7+ cells in human fetal tissues. We found that before T cell precursor colonization of the thymus (7-8 wk of gestation), CD7+ cells were present in yolk sac, neck, upper thorax, and fetal liver, and were concentrated in mesenchyme throughout the upper thorax and neck areas. By 9.5 wk of gestation, CD7+ cells were no longer present in upper thorax mesenchyme but rather were localized in the lymphoid thymus and scattered throughout fetal liver. CD7+, CD2-, CD3-, CD8-, CD4-, WT31- cells in thorax and fetal liver, when stimulated for 10-15 d with T cell-conditioned media and rIL-2, expressed CD2, CD3, CD4, CD8, and WT31 markers of the T cell lineage. Moreover, CD7+ cells isolated from fetal liver contained all cells in this tissue capable of forming CFU-T colonies in vitro. These data demonstrate that T cell precursors in early human fetal tissues can be identified using a mAb against the CD7 antigen. Moreover, the localization of CD7+ T cell precursors to fetal upper thorax and neck areas at 7-8.5 wk of fetal gestation provides strong evidence for a developmentally regulated period in man in which T cell precursors migrate to the epithelial thymic rudiment.

A 90-day inhalation toxicity study of raw shale oil in Fischer 344 rats

The potential health effects of a raw shale oil were evaluated in a 90-day inhalation study in Fischer 344 rats. Groups of 15 male and 15 female rats were exposed 6 hr/day, 5 days/week for 13 weeks to aerosol concentrations of 0, 56, 120, or 492 mg/m 3. In the high-dose group, 10 males and 7 females died prior to the termination of the study, most within the first 5 weeks of the experiment. A dose-dependent suppression in weight gain was seen in all of the shale oil-exposed groups. The failure to gain weight was associated with a variety of clinicopathologic abnormalities, including a dose-related decrease in red and white blood cells, with lowered plasma protein levels and increased serum alkaline phosphatase, and with total bilirubin levels in males. The exposure of the test animals to aerosolized raw shale oil was also associated with inflammatory and hyperplastic lesions in the lungs and upper respiratory tract, atrophy of the thymus and thymic-dependent portions of the peripheral lymphoid system, and bone marrow. These changes demonstrate that inhalation of raw shale oil aerosol can produce major organ toxicity similar to that found after exposure to other unrefined oil products.

A 90-Day Inhalation Toxicity Study of Raw Shale Oil in Fischer 344 Rats

A 90-Day Inhalation Toxicity Study of Raw Shale Oil in Fischer 344 Rats. GORDON T., STROTHER, D. E., CRAMER, D. V., AND GOODE, J. W. (1987). Fundam. Appl. Pharmacol. 9, 287–296. The potential health effects of a raw shale oil were evaluated in a 90-day inhalation study in Fischer 344 rats. Groups of 15 male and 15 female rats were exposed 6 hr/day, 5 days/week for 13 weeks to aerosol concentrations of 0, 56, 120, or 492 mg/m3. In the high-dose group, 10 males and 7 females died prior to the termination of the study, most within the first 5 weeks of the experiment. A dose-dependent suppression in weight gain was seen in all of the shale oil-exposed groups. The failure to gain weight was associated with a variety of clinicopathologic abnormalities, including a dose-related decrease in red and white blood cells, with lowered plasma protein levels and increased serum alkaline phosphatase, and with total bilirubin levels in males. The exposure of the test animals to aerosolized raw shale oil was also associated with inflammatory and hyperplastic lesions in the lungs and upper respiratory tract, atrophy of the thyrnus and thymic-dependent portions of the peripheral lymphoid system, and bone marrow. These changes demonstrate that inhalation of raw shale oil aerosol can produce major organ toxicity similar to that found after exposure to other unrefined oil products.

Bone marrow function. I. Peripheral T cells are responsible for the increased auto-antiidiotype response of older mice.

After immunization with trinitrophenyl (TNP)-Ficoll, mice produced both anti-TNP antibodies and auto-anti-idiotype (auto-anti-Id) antibodies specific for the anti-TNP antibody. Older animals produced more auto-anti-Id than did young animals. When mice were exposed to a normally lethal dose of irradiation while their bone marrow (BM) was partially shielded, they survived and slowly (6 wk) regained immune function, as indicated by the number of nucleated cells in their spleen and the in vitro primary plaque-forming cell (PFC) response of their spleen cells to TNP-treated aminoethylated polyacrylamide beads. Recovery is presumably the result of repopulation of the peripheral lymphoid system by cells originating in the BM. By enzyme-linked immunosorbent assay (ELISA), and by hapten-augmentable PFC assay, we show that, after recovery from irradiation with their BM shielded, old animals produce low auto-anti-Id responses, like those of young animals. The transfer of splenic T cells into mice irradiated with their BM shielded provided evidence that the magnitude of the auto-anti-Id response is controlled by the peripheral T cells. Thus, mice that received splenic T cells from aged donors produced high levels of auto-anti-Id while those that received splenic T cells from young donors produce low levels of auto-anti-Id.

Ultrastructural localization of 2,4-dinitrophenyl groups on draining lymph node cells of guinea pigs following skin painting with 2,4-dinitrochlorobenzene: I. Scanning immunoelectron microscopic studies.

ABSTRACTThe distribution of DNP groups on cells taken from draining lymph nodes of guinea pigs 12 hours after painting the skin with DNCB was examined by scanning immunoelectron microscopy using antibody directed against DNP groups with bacteriophage T4 as a visual marker. The studies showed that DNP groups were distributed on the surface of the cells, demonstrating some differences in distribution pattern among the cells. The incidence of cells on which DNP groups were detected was approximately 60% in the normal animals, higher than that detected by a previous immunofluorescent study. The incidence was markedly reduced to approximately 3% by pretreatment with tolerogen, DNBSO3Na. DNP groups were detected on the surface of the cells forming both rabbit red cell rosettes and complement coated red cell rosettes. It is suggested that DNCB penetrates through the skin into the lymphatics carrying lymph from the painted site and combines with cell membrane components in the peripheral lymphoid system.

Fatal disseminated herpesvirus hominis type 2 infection in an adult with associated thymic dysplasia

Disseminated herpesvirus hominis (HVH) type 2 infection, proved by viral isolation, is described in a previously healthy young woman. The clinical course was characterized by rapidly progressive hepatic failure leading to death 1 week after hospitalization. Postmortem examination showed involvement of many organs by HVH, most severe in the liver. The thymus gland showed dysplasia. It is suggested that this thymic alteration was congenital and was associated with a partial deficiency in cellular immunity, which permitted the patient's relatively long survival but ultimately rendered her susceptible to overwhelming viremia. Six adults with disseminated HVH infection, type unspecified but proved by viral isolation, were found in a review of the literature; predisposing factors (steroids, burns, Hodgkin's disease, malnutrition) existed in five patients. The thymus gland was not described, however, in the autopsy reports on any of the five patients who died. It is concluded that in order to initiate early antiviral therapy, HVH should be a diagnostic consideration in adults with hepatitis, particularly if skin or mucosal lesions are present. Furthermore, the central and peripheral lymphoid system of any patient who dies of a disseminated viral infection should be thoroughly examined.

Role of Thymosin and other Thymic Factors in the Development, Maturation, and Functions of Lymphoid Tissue

This chapter discusses the role of thymosin and other thymic factors in the development, maturation, and functions of lymphoid tissue. The thymus is the central organ in regulating the development and expression of cell-mediated immunity and general host resistance. The present evidence supports the concept that the thymus functions as both a donor of cell to the peripheral lymphoid system and by the production and secretion of one or more humoral factors. The mechanism by which the thymus exerts this apparent endocrine role and the number of hormones secreted by the thymus is in the early stages of exploration. The responses to partially purified thymic fractions of those functions of lymphoid tissue which are fundamental to host immunological competence suggests that several of the diverse crude thymic fractions may contain a single biologically active substance similar to or identical with thymosin. It is also established that the thymus is a major source of lymphocytes for the peripheral lymphoid tissues and circulation. Thus, the thymus exerts a dual function, namely, as an endocrine gland and as a progenitor of lymphoid cells.

Wasting Disease Induced with Cortisol Acetate

Summary The extent of immunologic impairment and time of immunologic recovery was studied in germfree mice following the neonatal administration of cortisol acetate. The hemolysin and hemagglutinin response to sheep erythrocytes was found to be markedly impaired for at least 30 days, but had fully recovered 50 days after cortisol treatment. The ability to reject tail skin allografts was fully developed 20 days after cortisol treatment. The recovery of the homograft reaction appeared to be related to the time of functional recovery of the thymus and peripheral lymphoid system. The ability of spleen cells from GF mice to elicit the GVH reaction was severely impaired for 10 days following treatment with cortisol. By day 30, the GVH reactivity of spleen cells from treated mice was comparable to that of control cells. The significance of these results obtained in germfree mice is discussed in relation to the role of the thymus and the normal bacterial flora in immunologic recovery.