Lymphopenia and Abnormal Lymphocyte Subsets in the “Bb” Rat: Relationship to the Diabetic Syndrome

Abstract

The "BB" rat spontaneously develops insulitis followed by impaired glucose tolerance (IGT) and/or an insulin-dependent diabetic syndrome like that in man. All diabetic rats in this study showed marked lymphopenia in blood, lymph nodes, spleen, and thymus. Peripheral blood lymphopenia antedated glucoregulatory disturbances. All rats showing either insulitis with or without IGT or diabetes were lymphopenic. None with normal lymphocyte counts developed any abnormality. Diabetics showed marked decrease in the proportions of T+ lymphocytes in all tissues. 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 was that which includes helper T lymphocytes. Thus: a) generalized lymphopenia most marked for T lymphocytes has been shown, b) helper T lymphocytes show proportionally the greatest reduction, c)thymic helper T deficit suggests a thymic origin of the lymphopenia, d) lymphopenia is a possible marker for susceptibility to the syndrome.

Coxsackievirus B4 infection of murine foetal thymus organ cultures

“…Altogether these data raise the question of the role of thymus disorders resulting from viral infections in the pathogenesis of type 1 diabetes. The role of alterations in T lymphocyte subsets in the development of the disease cannot be excluded in so far as they have been observed in NOD mice, BB rats and diabetic patients [Jackson et al, 1981;Poussier et al, 1982;Johnston et al, 1988;Faustman et al, 1991;Zipris et al, 1991]. Whether CV-B4-induced disturbances of thymic cells during foetal life can play a role in type 1 diabetes pathogenesis, by impairing T-cell differentiation, central self-tolerance and homeostasis, should be investigated further.…”

Lymphocyte transfusions prevent diabetes in the Bio-Breeding/Worcester rat.

“…Lymphocytopenia is also a characteristic immunologic abnormality of the BB rat (12,23,24,25). Although the total white blood cell count was not increased by transfusion, animals receiving white cell concentrate had a greatly increased percentage of OX 19 labeled circulating T lymphocytes.…”

Spleen cell transfusion in the Bio-Breeding/Worcester rat. Prevention of diabetes, major histocompatibility complex restriction, and long-term persistence of transfused cells.

“…Islet and other autoantibodies are detectable both before and after the onset of diabetes (5,6). The animal also exhibits depressed cell-mediated immune responses (2) due at least in part to a severe T cell lymphopenia (7,8).…”