Repeated large-volume blood withdrawals started at a young age previously appeared to correct lymphopenia and prevent diabetes in Ottawa diabetes-prone BB (BBdp) rats. Therefore, we sought an early effect 24 h after withdrawal of 25% of estimated blood volume and then reexamined the long-term effects in BBdp rats. The reexamination was prompted by the occurrence of variable numbers of BBdp rats positive for RT6.1 (a T-lymphocyte differentiation alloantigen) whose presence appears to “protect” against diabetes development (identified as BBp rats). Four groups were studied: non–diabetes-prone (BBn), RT6.1 BBdp, RT6.1+ BBp, and acutely diabetic BB (BBd) rats. An acute increase in the number of peripheral blood mononuclear cells and many subsets occurred in BBd and BBp rats. Despite these acute effects, a long-term effect of repeated blood withdrawal was not found in circulating cell counts or prevention of diabetes in BBdp rats. Thus, the previous finding was probably attributable to the presence of BBp rats. The long-term study demonstrated that RT6.1 expression in BBn rats increased from low levels at 15 days, peaked at 50 days, and decreased thereafter, an important finding in interpreting RT6.1 status at different ages. Furthermore, in contrast with other subsets, MARK-1+B lymphocytes and 0X42+ monocytes/macrophages decreased markedly in number at 120 and 150 days in BBn and BBp rats, whereas counts were higher and sustained in BBdp rats. The latter finding could be related to BBdp rats successfully resisting the autoaggressive process beyond the peak age of diabetes onset.

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