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C MARTINEZ

Publications and source records attributed to C MARTINEZ.

At least 37 records · Page 2Linked to original sources
PubMed1963

STUDIES ON THE ROLE OF THE THYMUS IN IMMUNOBIOLOGY; RECONSTITUTION OF IMMUNOLOGIC CAPACITY IN MICE THYMECTOMIZED AT BIRTH.

The immunologic competence of spleen cells of mice, as assessed by their graft versus host capabilities, increases to 35 days of age and beyond. Thymectomy at any point along this continuum of development produces "immunologic arrest;" the peripheral lymphoid tissues of such mice do not show significant increases in activity as the animals mature, nor is there appreciable loss of activity up to 6 months after surgery. Adult spleen cells from mice thymectomized at 1 to 24 hours of age have a greatly reduced ability to induce runt disease. Five million spleen cells from immunologically mature animals will uniformly cause fatal runt disease in neonatal recipients, but this same number of cells from neonatally thymectomized animals produces almost no runt disease. When the dosage of cells from neonatally thymectomized C(57)Bl mice is increased to 20 million, about half of the A recipients develop runt disease. Thus, the defect is a quantitative one. Spleen cells from neonatally thymectomized mice will induce tolerance of skin grafts from the donor strain. In one recalcitrant strain combination, C(57)Bl to A, use of spleen cells from neonatally thymectomized donors as the tolerance-inducing inoculum permits survival of the recipients, which usually die with severe runt disease, but does not induce tolerance. Cell free extracts of spleen and thymus tissue, including "promine" of Szent-Gyorgyi et al., did not affect the runting syndrome or the immunologic reactivity of neonatally thymectomized mice. When syngeneic thymic tissue is grafted into neonatally thymectomized mice, or the animals are given viable syngeneic spleen or thymus cells, the majority of the animals escape the early mortality characteristic of this group. Administration of syngeneic spleen cells from adult donors and grafting of syngeneic neonatal thymus provide restoration of homograft immunity and graft versus host reactivity of the peripheral lymphoid tissues in most of the neonatally thymectomized animals. Thymus cells rarely provide significant restoration of these parameters. Allogeneic thymus grafts also restore neonatally thymectomized mice. Such animals are chimeric: the immunologically competent cells of their peripheral lymphoid tissues are chiefly of host origin as determined by the discriminant spleen assay, but in many instances a significant donor component is also demonstrable in this system. These chimeric animals accept skin grafts from both donor and host strains. A degree of reconstitution has also been attained by grafting of allogeneic adult spleen in neonatally thymectomized animals. The discriminant spleen assay indicates that cells of the donor strain predominate in the peripheral lymphoid tissues of such mice.

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PubMed1963

PRODUCTION OF IMMUNOLOGICAL TOLERANCE IN MICE AFTER REPEATED INJECTIONS OF DISRUPTED SPLEEN CELLS.

1. Tolerance of male skin isografts has been regularly produced in female mice of the C57B1 strain sublines 1, 4, and 6 during adult life by repeated injection of completely disrupted spleen cells derived from male donors. The tolerant state is long-lasting since such grafts have remained in place more than 9 months. 2. Prolonged survival of homotransplants of skin has regularly been produced in DBA/2 mice during adult life by repeated injections of completely disrupted spleen cells from Balb/C donors. When injections of disrupted spleen cell material are continued over a sufficiently long period, permanent acceptance of the skin homografts may be obtained between these strains. 3. Immunological tolerance across even the strong H-2 histocompatibility barrier was obtained in the neonatal period and during adult life by repeated injection of disrupted spleen cell preparations. The tolerant state has been revealed by both mammary adenocarcinoma and skin homografting across this strong histocompatibility barrier. 4. In contradistinction to the tolerant state produced by injection of intact spleen cells in neonatal animals or during adult life or that produced by parabiotic union, the tolerance produced by repeated injection of disrupted spleen cell preparations cannot be transferred to syngenic neonatal mice with spleen cells of the tolerant animal. 5. The implications of these findings in transplantation biology and in consideration of the basic nature of tolerance are discussed.

Animals↗
PubMed1962

The role of the thymus in development of immunologic capacity in rabbits and mice.

In rabbits, complete thymectomy before the age of 5 days produced immunologic deficiency in the adult animals, as indicated by reduced antibody production to bovine serum albumin and bacteriophage T(2). Homotransplantation immunity was unaffected, however. In an inbred strain of mice, complete neonatal thymectomy resulted in complete inability of the 60-day-old animals to form antibody to bacteriophage T(2). Inbred mice, completely thymectomized at birth, had a deficient homograft response, indicated by acceptance of skin homografts from strains differing in both the weaker and stronger (H-2) histocompatibility antigens. Tumor transplants (mammary adenocarcinoma) were also successful across the H-2 genetic barrier in mice thymectomized at birth. Neonatal thymectomy also eliminated the Eichwald-Silmser phenomenon, rendering female mice capable of accepting isografts of male skin. Transplantation immunity in mice was also affected by later thymectomy, at 30 days of age, in certain strain combinations involving weak histocompatibility differences. Spleen and lymph node cells from mice thymectomized at birth or at 6 days of age, and sacrificed 2 months later, did not produce a graft versus host reaction in appropriate F(1) hybrid recipients, indicating that such cells are immunologically inactive. Neonatal thymectomy of F(1) hybrid mice, and in one strain combination thymectomy at 40 days of age, produced animals with inordinate susceptibility to runt disease (homologous disease) following injection of parent strain spleen cells 35 days (neonatal surgery) and 10 days (surgery at 40 days) later. Mice thymectomized at birth also showed growth failure and were short-lived. Studies of newborn mice indicated that they have true lymphocytes only in the thymus, and lack such cells in the spleen, lymph nodes, and gut. In normal mice, adult lymphoid structure develops gradually, beginning during the 1st week of life and continuing for the next month. In contrast, mice thymectomized at birth do not develop mature lymphoid structure: the lymph nodes and spleens tend to be small and poorly organized, and show a quantitative deficiency in lymphoid cells. It is our current working hypothesis that the thymus makes a major contribution toward the centrifugal distribution of lymphoid cells which, in turn, is essential to the full expression of immunologic capacity.

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