Passive transfer of insulitis and lymphopenia in the BB rat.

The BB rat spontaneously develops insulitis followed by impaired glucose tolerance (IGT) or an insulin-dependent diabetic (IDDM) syndrome. Passive transfer of insulitis from newly detected diabetic BB rats to nude mice has been achieved by intraperitoneal or intravenous injection(s) of blood and spleen lymphocytes. After a single injection of cells, 37% of the mice (n = 72) showed insulitis with a mean intensity of 1.9 +/- 0.3 (on a scale of 0 to 3). After three successive injections, 58% of the recipient mice (n = 12) showed insulitis with a mean intensity of 2.5 +/- 0.3. Only one of the control mice (n = 45) demonstrated mild insulitis. The small number of affected islets (13% after a single injection, 17% after three injections) probably explains the absence of random or post IP glucose hyperglycemia in the recipient mice. During this study the yield of lymphocytes in diabetic BB rats was found to be consistently lower than in control normal Wistar rats. This lymphopenia was found not only in the blood and the spleen but also in the thymus and the lymph nodes. Peripheral blood lymphopenia antedated glucoregulatory disturbances. All rats showing either insulitis alone or with IGT or IDDM were lymphopenic. None with normal lymphocyte counts developed any abnormality. Diabetics showed a marked decrease in the proportions of T+ lymphocytes in all tissues whereas the proportion of B(Ia+) lymphocytes was normal in blood, spleen, and thymus but increased in lymph nodes. However, in absolute terms both T+ and Ia+ lymphocytes were decreased. The subset decreased by the greatest proportion in all tissues, except in the thymus was the one that includes helper T lymphocytes. This lymphopenia could be related to the presence of circulating antilymphocyte antibodies. These results strongly support a role for altered immunity in the etiology of the syndrome. If the observed anomalies of lymphocyte numbers and subsets are responsible, then a novel mechanism different from most other "autoimmune" disorders must be implicated.