Comparative effects of a protein deprived diet on the weight, lymphocyte content and the number of DNA-synthesizing and dividing cells in the lymphoid organs of the rat. Influence of the diet on the stimulating action of phytohemagglutinin and the inhibitory action of cortisone.

The changes induced in adult male rats by a protein deprived (PD) diet lasting 7 weeks were investigated from the viewpoint of the cell contents of the popliteal lymph nodes (PLN), spleen and thymus; the levels of DNA-synthesizing lymphocytes counted on cell smear autoradiographs, and the levels of mitoses. The stimulating effect of a subplantar injection of phytohemagglutinin (PHA) and the inhibitory action of cortisone (3 mg/100 g per day for 5 days) were also determined in normal and PD rats. The PD diet significantly reduced the cell contents, primarily in the thymus, as well as the number of labeled cells and mitoses per mg of tissue and per entire organ. When expressed on the basis of 10(3) cells, the levels of both cell groups were also reduced in the spleen but not in the PLN's where they were already very low with a balanced diet. In the thymus, the sharp drop in the mitotic index (M.I.) contrasted with unchanged levels of labeled cells and an important increase in the labeling density per cell. PHA increased the M.I. to a great extent in the PLN's and spleen in normal rats but not in PD rats. In contrast, the labeling index (p. 10(3) cells) in the spleen, as well as the number of labeled cells per mg and per organ, increased in PLN's and the spleen after PHA to a much greater extent with a PD diet than with a normal diet. These results suggest a premitotic block of the cell cycle after protein deprivation. Also, the mitotic index appears to be a more reliable test, than the labeling index, of the lymphostimulating action of PHA and of its inhibition following protein removal from the diet. The effects of cortisone in normal rats resembled to a large degree those of a protein-free diet. If the hormone was administered to PD rats, the residual lymphocytes of the atrophic thymus were still more cortisone-sensitive than those of normal rats. On the contrary, DNA synthesizing cells in the PLN's and spleen, and mitoses in the spleen resisted cortisone in PD rats, while they were partly destroyed by the hormone in the controls. This suggests that primarily the cortisone-resistant lymphocytes of these organs are capable of synthesizing DNA after prolonged protein deprivation. The results are in agreement with the hypothesis of an intervention of endogenous glucocorticoid hormones in the protein lack-induced lymphoid involution.