T cell dysfunction in the diabetes-prone BB rat. A role for thymic migrants that are not T cell precursors

نویسندگان

  • H M Georgiou
  • A C Lagarde
  • D Bellgrau
چکیده

Diabetes-prone BB (BB-DP) rats express several T cell dysfunctions which include poor proliferative and cytotoxic responses to alloantigen. The goal of this study was to determine the origin of these T cell dysfunctions. When BB-DP rats were thymectomized, T cell depleted, and transplanted with neonatal thymus tissue from diabetes-resistant and otherwise normal DA/BB F1 rats, the early restoration of T cell function proceeded normally on a cell-for-cell basis; i.e., peripheral T cells functioned like those from the thymus donor. Because the thymus in these experiments was subjected to gamma irradiation before transplantation and there was no evidence of F1 chimerism in the transplanted BB-DP rats, it appeared that the BB-DP T cell precursors could mature into normally functioning T cells if the maturation process occurred in a normal thymus. If the F1 thymus tissue was treated with dGua before transplantation, the T cells of these animals functioned poorly like those from untreated BB-DP rats. dGua poisons bone marrow-derived cells, including gamma radiation-resistant cells of the macrophage/dendritic cell lineages, while sparing the thymic epithelium. Therefore, the reversal of the T cell dysfunction depends on the presence in the F1 thymus of gamma radiation-resistant, dGua-sensitive F1 cells. Conversely, thymectomized and T cell-depleted F1 rats expressed T cell dysfunction when transplanted with gamma-irradiated BB thymus grafts. T cell responses were normal in animals transplanted with dGua-treated BB thymus grafts. With increasing time after thymus transplantation, T cells from all animals gradually expressed the functional phenotype of the bone marrow donor. Taken together these results suggest that BB-DP bone marrow-derived cells that are not T cell precursors influence the maturation environment in the thymus of otherwise normal BB-DP T cell precursors.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Recapitulation of normal and abnormal BioBreeding rat T cell development in adult thymus organ culture.

Congenitally lymphopenic diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous T cell-dependent autoimmunity. Coisogenic diabetes-resistant (DR) BB rats are not lymphopenic and are free of spontaneous autoimmune disease, but become diabetic in response to depletion of RT6+ T cells. The basis for the predisposition to autoimmunity in BB rats is unknown. Abnormal T cell development in DP-...

متن کامل

High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats.

Diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous autoimmune diabetes. DP-BB thymocyte export is reduced, and most thymic emigrants disappear rapidly from peripheral lymphoid tissues. DP-BB rats are consequently lymphopenic and circulate severely reduced numbers of T cells. Peripheral T cells present are phenotypically immature (Thy1+) and appear activated. We hypothesized that DP-B...

متن کامل

Nucleotide and deduced amino acid sequence of the rat T-cell alloantigen RT6.1.

The rat T-cell alloantigenic system RT6 comprises two known alleles, RT6 a and RT6 b. The respective protein products, designated RT6.1 and RT6.2, are expressed on mature peripheral T-cells of the rat, but not on thymocytes or recent thymic migrants (1—3). Diabetes-prone BB rats are deficient in RT6 expression, and this defect has been correlated with the pathogenesis of autoimmune insulin-depe...

متن کامل

Identification of a limited T-cell receptor beta chain variable region repertoire associated with diabetes in the BB rat.

Diabetes-prone BB rats spontaneously develop type 1 diabetes due to a T-cell-dependent destruction of insulin-producing beta-islet cells. A number of T-cell abnormalities including lymphopenia, poor cell-mediated responsiveness to alloantigen, and an absence of an RT6+ T-cell subset are associated with disease susceptibility. Our previous studies have implicated the thymic antigen-presenting ce...

متن کامل

INDUCTION OF TYPE 1 DIABETES IN DIABETES-RESISTA NT (BB-DR) RATS

The BioBreeding- Diabetes Prone (BB-DP) rat spontaneously develops an autoimmune diabetic syndrome that is dependent on the RT1 u Major Histocompatibility Complex (MHC) haplotype and homozygosity for an allele at the Lymphopenia (Lyp) locus. Lyp mutation is responsible for a peripheral T -lymphopenia. There are other genetic loci contributing to diabetes susceptibility in this strain. BB ra...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 167  شماره 

صفحات  -

تاریخ انتشار 1988