SUMMARYWhen compared with laboratory chow, a defined, semipurified diet prevented diabetes, reduced the frequency of insulitis, increased thymus weight and total white blood cell count, and doubled thymus T-helper/T-suppressor cell ratios in diabetes-prone BB rats. These data show that the diabetic syndrome in BB rats may be prevented or delayed by changes in diet, which may occur through alteration of pathogenic defects in the immune system. DIABETES 1985; 34:1059-62.T he fact that only up to 50% of unaffected twins of individuals with type I, insulin-dependent diabetes mellitus (IDDM) become diabetic underscores the major role of environmental factors in the expression of this genetically transmitted disease. With the exception of tropical malnutrition diabetes, a unique ketosis-resistant form of IDDM in which there is an acknowledged involvement of diet, 1 there are no data directly linking diet to incidence of type I IDDM in humans. 2 The two main obstacles have been the inability to identify prospective diabetic humans and the inherent difficulties in obtaining accurate and representative dietary information.The recent availability of the spontaneously diabetic BB rat has provided a unique model that has many of the features of human type I diabetes, permitting long-term prospective studies to be carried out. 34 BB rat diabetes appears to be an autoimmune disease resulting from the destruction of the insulin-producing beta cells of the pancreas by the animal's own immune system. Development of overt diabetes may require inheritance of at least three characteristics: mononuclear cell infiltration of the pancreas (insulitis), the pres- ence of the major histocompatibility complex haplotype (RT1 U ), and lymphopenia. 56 The protective effect of neonatal thymectomy, 78 decreased thymus (T)-derived lymphocytes in blood and lymphoid organs, 9 reduced T-helper (T h )/T-suppressor (T s ) cell ratios, 6 and decreased thymus weight in diabetes-prone BB rats all point to a key role for the thymus in the pathogenesis of this syndrome.Diet can have dramatic effects on the immune system, particularly the thymus, which seems uniquely sensitive to manipulation of nutritional variables. 10 Furthermore, it has recently been hypothesized that environment (diet) could be an important factor influencing development of diabetes in BB rats. 811 In previous studies we observed differences in incidence and age at onset, which suggested that, compared with a chow diet, a defined, semipurified AIN-76 diet 12 might modify development of the syndrome. 8 Any approach to this question must consider at least three points: (1) effect of diet on insulitis, diabetes incidence, age at onset; (2) net diet/ immune system interactions (i.e., varying susceptibility of specific T-cell subsets); and (3) presence or absence of diabetogens in the diet. MATERIALS AND METHODSExperiment 1. This experiment was designed to examine directly the effects of ad libitum feeding of a ground laboratory rat chow diet (N = 40) or a defined, semipurified AIN-76 ...

Fifty-nine HIV-1 antibody positive and 58 antibody negative hemophiliacs were evaluated over a 2 year study period to gain insight into the natural history and prognosis of HIV-1 disease in members of this risk group. Mean CD4 (Leu 3+) cell counts calculated at 6 month intervals decreased gradually in seropositive patients (from 403 to 311/microliters) whereas CD8 (Leu 2+) counts remained stable but above the normal range. CD4 cell counts correlated closely with advancing CDC clinical stage; CD8 numbers showed no such association, but were markedly lower in the six patients with overt AIDS. Serum P24 antigenemia was associated with low CD4 cell counts and with advanced clinical stage (58% of antigenemic and 14% of non-antigenemic seropositive patients were in stage IV). In addition to CD4 cell counts, significant reductions in Leu 11+ natural killer cell (NK) subsets and in Leu 3 + 8 - cells occurred in seropositive patients over the study period; Leu 2 + DR + cells increased significantly. When expressed as a percentage of lymphocytes, the reduction in Leu 19 + NK cells was also significant, as were the increases in Leu 4 + DR + cells and Leu 12 + 8 + B cells. In summary, declining CD4 cell numbers and percentages are valuable markers of progressive HIV-1 disease in hemophiliacs, but may not always accurately reflect the degree of disease activity. Progressive changes in additional variables such as serum P24 antigen, and numbers and percentages of NK cell subsets and (as AIDS supervenes) CD8 cell numbers, may allow more precise monitoring of HIV-1 disease. This will, in turn, facilitate the design of optimal individualized strategies for therapeutic intervention.

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The immune competence of peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus-seropositive (HIV+) patients was studied by assessing cytotoxic T lymphocyte (CTL) activity following recall HIV antigen stimulation. Target cells were HLA-A-matched EBV-transformed B cells expressing HIV-1 antigen. In the presence of recombinant IL-2 (rIL-2, 2 or 10 U/ml), about 50% of PBMCs from HIV+ asymptomatic patients responded to HIV-1 antigen stimulation in vitro with increased cytotoxic activity. In contrast, PBMCs from patients with overt AIDS, cultured in medium containing rIL-2 (2 U/ml) and HIV-1 antigen, showed no increase in cytotoxic activity; in the presence of rIL-2 (10 U/ml) and HIV-1 antigen, an inhibitory effect on CTL activity was observed. This inhibitory effect was associated with programmed cell death (apoptosis) of CD8+ lymphocytes and cells of both gamma/delta TcR-positive and -negative phenotypes. However, prior to the apoptosis, different TcR phenotypes of T lymphocyte reacted differently to HIV-1 antigen stimulation. The HIV-1 antigen initially appeared to cause gamma/delta TcR-positive T lymphocytes to proliferate and/or differentiate and later induced cell death. Whereas, prior to the apoptosis, no proliferation of gamma/delta TcR-negative T lymphocytes induced by HIV-1 antigen was observed.