The Thymus and Autoimmune Disease

Peptides containing a dominant T-cell epitope from red cell band 3 have in vivo immunomodulatory properties in NZB mice with autoimmune hemolytic anemia

“…Another possibility is that there may be a generalized deficit in the ability to generate autoantigenspecific regulatory T cells in the autoimmune-prone NZB strain, which displays a number of other autoimmune abnormalities, such as elevated levels of immunoglobulin, anti-DNA antibodies, antithymocyte antibodies, and circulating immune complexes, in addition to AIHA. [3][4][5] A switch to a suppressive subset would be expected to be more effective therapeutically than the deviation toward a Th2 response seen in NZB mice that had received peptide 861-875 (Glu861, Lys875). In this respect it is noteworthy that the dominant human RBC autoantigens, the Rh proteins, carry epitopes that stimulate IL-10 production by T cells from AIHA patients.…”

“…4 It has been debated whether the production of this antibody is T-cell dependent. Early work showed that neonatal thymectomy failed to prevent the generation of RBC autoantibodies 5 and that NZB bone marrow cells could transfer RBC autoantibody production to an irradiated H-2-matched healthy strain, even if the recipients were chronically T-cell depleted. 4 More recently, it was demonstrated that oral administration of lipopolysaccharide activated B-1 cells and led to the production of autoantibody in trangenic mice expressing a pathogenic IgM monoclonal antibody derived from NZB mice.…”

Relative Inability to Induce Tolerance in Adult NZB and NZB/NZW F1 Mice

“…DeVries and HJjmans (24) described changes in thymic epithelial cells and Hassall's corpuscles in young NZB and B/W mice during the latent phase of their disease prior to the onset of serologic abnormalities. Neonatal thymectomy in NZB mice did not delay the onset of autoimmune hemolytic anemia or Coomb's positivity but rather hastened them (25,26), while thymectomy in rabbits (27) and Swiss mice (28) led to the development of Coomb's positive reactions and antinuclear autoantibodics respectively. It is therefore tempting to speculate that the thymic histologic changes in NZB and B/W mice have as a functional counterpart the loss of a thymic function necessary for the induction of both experimentally induced and self-tolerance.…”

Transfer of spleen cells from young to aging NZB × NZW F1 hybrid mice. Effect on mortality, antinuclear antibody, and renal disease

“…This investigation differs from previous studies of the effects of young New Zealand mouse lymphocytes on suppressor activity and autoimmune disease (10)(11)(12)14,16,(17)(18)(19) in two respects: a) Young spleen lymphocytes were administered over a prolonged period to aging BW mice that had not had prior thymectomy or ALG treatment. b) The effect of the transferred lymphocytes on renal histopathology was evaluated.…”

“…The severity of the autoimmune disease in thymectomized (10)(11)(12)14) or antilymphocyte globulin (ALG)-treated (12) BW and NZB mice has been observed to decrease after injection of spleen or thymus lymphocytes from young syngeneic mice. The effects of young lymphoid cells on a postulated suppressor cell deficiency in old BW and NZB mice have been evaluated (13,16).…”