Regeneration of Thymus Grafts. I. Histological and Cytological Aspects

Dukor, P.; Miller, J. F. A. P.; House, Winifred; Allman, Violet

doi:10.1097/00007890-196509000-00006

Cited by 128 publications

(56 citation statements)

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“…These transfer experiments were, however, performed 30 days after irradiation and thymus grafting. It is known that, at that time, the lymphoid cell population of the graft has been replaced entirely by cells derived from the bone marrow (12). Thus hemolysins detected in irradiated mice, presensitized against thymus donor-type cells, may have been produced by bone marrow-derived cells which had repopulated, and migrated from, the thymus graft.…”

Section: Discussionmentioning

confidence: 99%

Cell to Cell Interaction in the Immune Response

Mitchell

Miller

1968

The Journal of Experimental Medicine

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585

122

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An interaction between thymus or thoracic duct cells and antibody-forming cell precursors has been implicated in the response of mice to sheep erythrocytes (1). The possibility was raised that the thymus contributes cells to the circulating pool of lymphocytes which recognize antigen (ARC) and which influence the differentiation of antibody-forming cell precursors (AFCP) to hemolysin-forming cells. The experimental system employing reconstituted neonatally thymectomized mice failed to detect the existence of AFCP in inoculated lymphoid cell suspensions.Previous work from this laboratory (2) had demonstrated that thoracic duct and spleen cells were capable of affecting the appearance of hemolytic foci in the spleens of heavily irradiated recipients injected with sheep erythrocytes. If such loci represent clusters of antibody-forming cells, then either the inoculum must contain cells potentially capable of producing hemolysins, or the host must provide AFCP which are extremely radio-resistant.In this paper, we present the results of experiments designed to determine whether both ARC and AFCP are present in populations of cells from thymus, thoracic duct lymph, or bone marrow. Materials and MethodsA,imals.--Mice of the highly inbred strains CBA and C57BL, and Ft hybrids from crosses between these strains were used. The origin and maintenance of these mice have been described in the previous paper (1).Cell suspensions were prepared as before (1). 0t~¢ra~i~e Procedures.--Thymeetomy or sham operation was performed in young adult mice, 4--6 wk old, as previously described (3). Checks for the presence of thymus remnants

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Section: Discussionmentioning

confidence: 99%

Cell to Cell Interaction in the Immune Response

Mitchell

Miller

1968

The Journal of Experimental Medicine

Self Cite

585

122

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“…4 However, it is known that the lymphocyte population of a thymus graft in a marrow-protected irradiated host is entirely replaced within two to three weeks by cells from the inoculated marrow. 3 Hence, although antibody-forming cells had the genotypic characteristics of the marrow donor, they could have been derived from cells that had first migrated through the thymus implant which, in these experiments, had been grafted 30 days prior to antigenic stimulation. Such an experimental design therefore failed to establish unequivocally which cell type was the immediate precursor of the antibody-forming cell: thymus or marrow cell.…”

mentioning

confidence: 99%

Immunological activity of thymus and thoracic-duct lymphocytes.

Gf¹,

Miller²

1968

Proc. Natl. Acad. Sci. U.S.A.

236

103

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The reduced immunological responsiveness of neonatally thymectomized rodents has been reversed far more effectively with cells from spleen, lymph nodes, and thoracic-duct lymph than with cells from either thymus or bone marrow.' In heavily irradiated mice, an inoculum containing a mixture of marrow and thymus cells allowed the production of more hemolysins against sheep erythrocytes than could be accounted for by summating the activities of each cell population alone.2 Some type of interaction must thus take place between thymus cells, bone marrow cells, and antigen. In order to characterize the nature of this interaction one would first have to determine which cell type, thymus or bone marrow, was the immediate precursor of the antibody-forming cell.In thymectomized irradiated mice protected with chromosomally marked bone marrow and grafted with chromosomally marked thymus tissue, both marrowdonor-type and thymus-donor-type cells were found dividing in the lymphoid tissues. The majority of dividing cells were of marrow donor origin,3 but a sharp increase in the proportion of thymus-derived cells occurred for a short period of time after antigenic stimulation.4 An attempt was made to determine the origin of the antibody-forming cell by using a transfer system in which both chromosome and isoantigenic markers were available. The results indicated that, although thymus-graft derived cells responded vigorously to antigenic stimulation by mitosis, the antibody-forming cells had the immunogenetic characteristics of the marrow donor.4 However, it is known that the lymphocyte population of a thymus graft in a marrow-protected irradiated host is entirely replaced within two to three weeks by cells from the inoculated marrow.3 Hence, although antibody-forming cells had the genotypic characteristics of the marrow donor, they could have been derived from cells that had first migrated through the thymus implant which, in these experiments, had been grafted 30 days prior to antigenic stimulation. Such an experimental design therefore failed to establish unequivocally which cell type was the immediate precursor of the antibody-forming cell: thymus or marrow cell.In our laboratory we have attacked the problem by using cell suspensions rather than thymus grafts. A mixture of thymus and bone marrow cells from unrelated strains of mice was inoculated together with sheep erythrocytes into irradiated hosts. Under these conditions no hemolysin response was obtained, I suggesting that interaction does not take place between allogeneic cells immediately upon transfer to irradiated recipients. Neonatally thymectomized mice were then used as hosts of syngeneic or allogeneic thymus cells injected together with sheep erythrocytes. Since the marrow of neonatally thymectomized rodents 296

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“…Regenerative processes in neonatal thymus grafts were observed histologically and cytologically by DUKOR et al (1965). A sequence of weight changes in thymus grafts was reported by METCALF (1965).…”

Section: Discussionmentioning

confidence: 98%

“…aspects of thymus grafts in mice (METCALF, 1963(METCALF, , 1964DUKOR, MILLER, HOUSE and ALLEN, 1965;LEUCHARS, CROSS and DUKOR, 1965;MILLER et al, 1966). In these studies, thymuses from neonatal donor mice were usually grafted under the renal capsule of recipients, because grafting at that site offered many advantages as compared with other sites.…”

mentioning

confidence: 99%