scholarly journals STUDIES ON THYMUS FUNCTION

1970 ◽  
Vol 132 (3) ◽  
pp. 583-600 ◽  
Author(s):  
Osias Stutman ◽  
Edmond J. Yunis ◽  
Robert A. Good

Immunological restoration of 45-day old, neonatally thymectomized C3Hf mice by treatment with humoral thymic function (thymoma grafts, thymus or thymoma in diffusion chambers) ranges from 0 to 12% and is difficult to acheive. When small numbers (5–20 x 106) of young adult lymphohemopoietic cells, ineffective by themselves, are given in association with humoral thymic function, a cooperative effect is observed and restoration ranges from 30 to 60%. With a particular cell dosage (20 x 106), effectivity for cooperation with thymic function was the following in decreasing order: spleen, lymph nodes, thoracic duct cells, bone marrow, blood leukocytes, thymus, and Peyer's patch cells. Comparable results were obtained using spleen, thymus, and hemopoietic liver from newborn donors in association with thymic function. For similar cell dosages, newborn thymus cells were more effective than adult thymus in their cooperative effect with thymic function. Dispersed thymus cells in association with young adult bone marrow or newborn hemopoietic liver cells showed no synergism for the cooperative effect with thymic function in the present model. Using hemiallogeneic cells (F1 hybrid into parent) it was possible to show that restoration was mediated by proliferative expansion of the injected cells. This was indicated by specific tolerance to tissues of the other parental strain and by cellular chimerism, especially of lymphoid tissues, as indicated by chromosome markers and absence of significant numbers of immunocompetent cells of host origin. A population of paritally differentiated cells of hemopoietic origin, termed postthymic, sensitive to humoral activity of the thymus and present in the lymphohemopoietic tissues of adult and newborn mice is postulated to explain our results. These cells are postthymic and thymus dependent in the sense that they already received thymic influence, probably through traffic, and are incapable of self-renewal in absence of the thymus. Sensitivity to humoral activity of the thymus is characterized by proliferative expansion and/or a differentiative process eventually leading to larger numbers of competent cells.

1973 ◽  
Vol 137 (2) ◽  
pp. 461-469 ◽  
Author(s):  
J. Louis ◽  
J. M. Chiller ◽  
W. O. Weigle

Antigen-binding cells (ABC) to the antigen human gamma globulin (HGG) were quantitated in lymphoid tissues of A/J mice at various times after the injection of deaggregated HGG (tolerogen), aggregated HGG (immunogen), or saline. The reaction of lymphoid cells with highly labeled HGG was specific to that antigen since binding could be inhibited by excess unlabeled HGG, but not by unrelated non-cross-reacting proteins. Compared with normal mice, there was a marked decrease in the numbers of ABC in the spleens of unresponsive animals evident as early as 12 h after the injection of tolerogen. A marked increase in ABC was observed in the spleens of immunogen-injected mice, beginning at 24 h and reaching a peak at 3 days. In bone marrow, no difference in the number of ABC was found among the three experimental groups until day 20, when a reduction in ABC was observed only in tolerogen-injected mice. No quantitative difference in the thymuses in the experimental groups could be determined because of the paucity of ABC displayed by normal thymus cells.


1974 ◽  
Vol 140 (5) ◽  
pp. 1285-1302 ◽  
Author(s):  
Edmond A. Goidl ◽  
Gregory W. Siskind

The ontogeny of the ability of B lymphocytes to produce an antihapten response which is heterogeneous with respect to affinity for the antigenic determinant was studied in a cell transfer system. The heterogeneity of affinity of the immune response of lethally irradiated mice reconstituted with syngeneic, adult thymus cells and fetal or neonatal tissues as a source of B lymphocytes was studied. It was found that B cells from 17 day fetal liver or neonatal liver are highly restricted with respect to heterogeneity of affinity as compared with adult spleen or bone marrow. The B-cell population achieves an adult character with respect to heterogeneity of affinity by 2 wk of age. The peripheral lymphoid tissues (spleen) appear to mature in this respect more rapidly than do central lymphoid tissues (bone marrow). Spleens from 10-day old donors behave in an adult, heterogeneous manner while bone marrow from the same donors exhibit a marked restriction in heterogeneity of affinity. Germfree mice produce an immune response which is indistinguishable from conventionally reared adult animals with respect to heterogeneity of affinity. The earlier appearance of the ability to transfer a heterogeneous immune response in spleen as compared with bone marrow suggests that the increasing heterogeneity of the B-lymphocyte population which occurs between birth and 2 wk of age is the result of a differentiation event and not of a somatic mutation or recombination event.


1970 ◽  
Vol 132 (3) ◽  
pp. 601-612 ◽  
Author(s):  
Osias Stutman ◽  
Edmond J. Yunis ◽  
Robert A. Good

Significant immunological restoration of 45-day old, neonatally thymectomized C3Hf mice was obtained by the cooperation of syngeneic newborn or embryonic hemopoietic liver cells with thymic function. Thymic function or cells alone are almost ineffective or restore approximately 10% of the animals. Newborn liver cells are effective in association with thymus grafts or humoral thymic function (thymoma grafts and thymus or thymomas in diffusion chambers). Embryonic liver cells are ineffective, even in large numbers, when associated with humoral thymic function. On the other hand, embryonic liver cells are effective in the cooperative effect only in association with viable thymus grafts, preferably syngeneic, whether the grafts were placed subcutaneously, intraperitoneally, or under the kidney capsule. Dispersed viable thymic cells are ineffective in association with embryonic liver cells. Cells capable of cooperating with humoral thymic function start to appear to embryonic liver by day 19–21 of gestation and are detectable until day 5–6 postbirth. Embryonic hemopoietic liver cells from 12 to 18 days of gestation contain cells capable of cooperation only with viable free thymus grafts and not with humoral thymic function. A prethymic cell population of partially differentiated cells of hemopoietic origin, insensitive to humoral activity of the thymus but requiring thymic stroma and traffic through the thymus is postulated to explain our results. This population of prethymic cells can become postthymic through this process and eventually develop into competent cells. Postthymic cells are characterized by their sensitivity to humoral activity of the thymus and by their wide distribution in the lymphohemopoietic tissues of newborn and young adult mice.


1963 ◽  
Vol 204 (2) ◽  
pp. 265-267 ◽  
Author(s):  
Leonard J. Cole

The capacity of intravenously injected cells from peritoneal fluid, peripheral blood, lymph nodes, thymus, and bone marrow of mice to restore hematopoiesis in lethally X-irradiated (880 rad) isogenic recipients, was investigated. Thirty-day survival and visible colony formation in the spleen were employed as the criteria. Administration of 6 x 106 or 11 x 106 peritoneal cells, and 6.4 x 106 or 15 x 106 peripheral leukocytes afforded protection against mortality, and elicited colonies in the spleen; comparable effects were observed after injection of 1.1 x 105 marrow cells. The injection of 34 x 106 adult lymph node cells or of 9 x 106 thymus cells from newborn mice had no effect on mortality, nor did they elicit spleen colony formation. A correlation appears to exist between the capacity of isogenic cells to restore hemopoiesis in lethally irradiated mice, and their ability to elicit visible colony formation in the spleen. Evidently normal peritoneal cell populations and peripheral blood leukocytes contain hemopoietic stem-cell elements, with a frequency 30–50 times lower than among bone marrow cells. No evidence was adduced to support the concept that normal lymphoid tissue lymphocytes give rise to hemopoietic cell lines.


1970 ◽  
Vol 132 (2) ◽  
pp. 317-328 ◽  
Author(s):  
Henry R. Hilgard

Graft-versus-host splenomegaly may be elicited from 500 R X-irradiated F1 hybrid hosts if the hosts are injected with bone marrow cells and thymus cells from parental strain donors. Cells from thymus only or bone marrow only will not elicit graft-versus-host splenomegaly in these hosts. In this requirement for cells from both sources, the bone marrow cells play a nonimmunologic, proliferative role in the splenomegaly, and the thymus cells carry out the immunologic attack. Thus the mechanism of this synergism is quite different from that reported for the humoral immune response to sheep erythrocytes in which both thymus and marrow interact in the production of the specific immunologic response itself.


1970 ◽  
Vol 131 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky

The capacity of cells from different lymphoid tissues obtained from Balb/c mice to produce graft-vs.-host (GVH) reactions was quantitatively determined in C57BL/6N by Balb/c F1 hybrid recipients. Synergistic responses were observed when small numbers of cells from lymphoid tissues that were rich in GVH activity such as spleen and femoral lymph node were combined with weakly reactive thymus cells. Thymus and spleen cells obtained from 1-wk old mice were separately inactive but produced moderate GVH reactions when combined in equal proportions. GVH activity of spleen cells from mice thymectomized at 3 days of age was partially restored by the addition of small numbers of spleen or thymus cells from adult mice. Changes in ratio between the two cell populations markedly affected the degree of synergy. Synergy was not observed when Balb/c cells were combined with Balb/c x C57BL/6N F1 hybrid cells and inoculated into C57BL/6N recipients, but was demonstrated when Balb/c and C57BL/6N cells were combined and inoculated into F1 recipients, indicating that a genetic disposition to mount GVH reactions in both populations is required to produce synergy. The data indicate that at least two cell types are necessary for GVH reactions, and that synergy between cell populations results from favorable adjustments in the ratio between these two cell types.


2021 ◽  
Vol 86 ◽  
pp. 102508
Author(s):  
Melissa Azul ◽  
Surbhi Shah ◽  
Sarah Williams ◽  
Gregory M. Vercellotti ◽  
Alexander A. Boucher

Blood ◽  
1975 ◽  
Vol 46 (5) ◽  
pp. 723-734 ◽  
Author(s):  
RT Parmley ◽  
M Ogawa ◽  
CP Jr Darby ◽  
SS Spicer

Abstract A child with congenital neutropenia was studied using bone marrow culture and ultrastructural and cytochemical techniques. The patient's marrow cells formed a large number of granulocytic colonies of normal size in culture, and her peripheral blood leukocytes produced adequate colony-stimulating factor. No serum inhibitors were identified. The patient's promyelocytes from direct marrow and culture appeared normal in ultrastructure, and primary granules, contained peroxidase and acid phosphatase activity. Myelocytes and rare segmented neutrophils from direct marrow specimens demonstrated atypical notched nuclei, myelin figures in Golgi lamellae and primary (azurophilic) granules, and no identifiable secondary (specific) granules. These data indicate an intrinsic neutrophil defect which allows normal proliferation of precursor cells, but results in abnormal granulogenesis and apparent inability to form secondary granules.


1971 ◽  
Vol 133 (6) ◽  
pp. 1325-1333 ◽  
Author(s):  
Klaus-Ulrich Hartmann

Spleen cells of bone marrow chimeras (B cells) and of irradiated mice injected with thymus cells and heterologous erythrocytes (educated T cells) were mixed and cultured together (17). The number of PFC developing in these cultures was dependent both on the concentration of the B cells and of the educated T cells. In excess of T cells the number of developing PFC is linearly dependent on the number of B cells. At high concentrations of T cells more PFC developed; the increase in the number of PFC was greatest between the 3rd and 4th day of culture. Increased numbers of educated T cells also assisted the development of PFC directed against the erythrocytes. It is concluded that the T cells not only play a role during the triggering of the precursor cells but also during the time of proliferation of the B cells; close contact between B and T cells seems to be needed to allow the positive activity of the T cells.


1985 ◽  
Vol 161 (3) ◽  
pp. 475-489 ◽  
Author(s):  
S H Lee ◽  
P M Starkey ◽  
S Gordon

We have estimated the macrophage content of different tissues of the normal adult mouse using F4/80, a highly specific antigen marker for mature mouse macrophages. An absorption indirect binding assay was used to quantitate F4/80 antigen against a calibration standard made from the J774.2 macrophage-like cell line. The richest sources of tissue F4/80 antigen were found to be bone marrow, spleen, cervical and mesenteric lymph nodes, large bowel, liver, kidneys, and small bowel. The organs that have the highest total F4/80 antigen content are the liver, large bowel, small bowel, bone marrow, spleen, cervical and mesenteric lymph nodes, and kidney. We conclude that the mononuclear phagocyte system is mainly distributed in the gastrointestinal tract and liver, followed by hemopoietic and lymphoid tissues.


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