Abrogation of peripheral tolerance in transgenic mice that express a uniform B-cell receptor may create a powerful tool to examine the molecular mechanisms that underlie the autoimmune response in B cells. Here we report that processes that induce a systemic lupus erythematosus-like syndrome in normal mice, namely chronic graft vs host reaction, trigger systemic autoimmunity in a well-establish...

Graft-t'ersws-host reactions, which may occur following the inoculation of immunologically competent cells into susceptible antigenic hosts, initiate a complex immunopathologic syndrome. The most characteristic feature of this experimental disease is widespread involvement of lymphoid tissue, typified by an early proliferative phase followed by varying degrees of lymphoid de pletion and atrophy...

Two experimental models have been used to study T-cell differentiation. The first, a graft-vs.-host reaction, was induced by injecting thymocytes or cortisone-resistant thymocytes into lethally irradiated allogeneic mice. The second was tumor graft rejection in allogeneic hosts. Ultrastructural studies at various time intervals revealed two differentiated T-cell types. One of these (the "pale" ...

Systemic lupus erythematosus (SLE) is an immune-mediated disease characterized by the presence of autoantibodies and a wide array of clinical symptoms. Despite intensive research, the aetiology of SLE is still unknown and is probably multifactorial. Both genetic and environmental factors have been associated with SLE, but these factors alone are insufficient to explain the onset of SLE. Recentl...

Introduction into the rabbit's anterior chamber of lymphoid cells sensitized to the histocompatibility antigens of the recipient leads to the development of an intraocular graft versus host reaction. This takes the form of a more-or-less severe uveitis, and the production of small focal areas of endothelial cell destruction on the posterior surface of the cornea. In the milder responses, these ...

A model system in AKR mice for the induction and cure of a clinically evident graft-versus-host disease is reported. Graft-versus-host disease is inititated by i.p. injections of ecyclophosphamide (250 mg/kg body weitht ) into female AKR mice, on Day 0. This is followed by i.v. injections of 45 x 10-6 normal spleen cells (NSC) from male C57BL/6J mice. Median survival time for these mice is 33.4...

In clinical practice, hematopoietic cell transplantation (HCT) is now recognized as a powerful means of delivering effective cellular immunotherapy for malignant and non-malignant diseases. In patients with severe hematological malignancies, the success of allogeneic HCT is largely based on immunologic graft-versus-tumor (GVT) effects mediated by allogeneic T lymphocytes present in the graft. U...

LTHOUGH the thymus has been proved to play an essential role in the development and maintenance of immune reactivity, the mechanisms by which it exerts these functions are still to be elucidated. While significant titers of antibody”2 or plasma cell accumulation3’4 have not been detected in the intact thymus of animals given antigens at distant site, histologic signs indicative of local antibod...

Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance. Based on demonstrated pro-tolerogenic activity, sirolimus (rapamycin) is an agent with promise to achieve these goals. In a long-term follow-up analysis of a randomized phase II trial comparing si...

LTHOUGH the thymus has been proved to play an essential role in the development and maintenance of immune reactivity, the mechanisms by which it exerts these functions are still to be elucidated. While significant titers of antibody”2 or plasma cell accumulation3’4 have not been detected in the intact thymus of animals given antigens at distant site, histologic signs indicative of local antibod...