SummaryMalnutrition continues to be a major public health problem throughout the developing world. Nutritional deficiencies may be the most common cause of secondary immunodeficiency states in humans. It has been suggested that nutritional imbalances can induce apoptosis in a variety of cell types. The purpose of this study was to examine the effect of severe malnutrition on cell subsets and the frequency of spontaneous and/or dexamethasone-induced cell death in vivo in the thymus and spleen from severely malnourished, lactating rats. Apoptosis frequency was estimated by flow cytometry using annexin-V and terminal transferase-mediated dUTP nick-end labelling assay assays. The results obtained in the present study indicate that malnutrition is associated with a significant increase of spontaneously apoptotic cells in the thymus (9·8-fold) and spleen (2·4-fold). Increase in apoptosis was associated largely with CD4 + CD8 + double-positive thymocytes. Unexpectedly, similar frequencies of spontaneous apoptosis of these cells were found in both wellnourished and malnourished rats. In contrast, consistent increases in the apoptosis of CD4 -CD8 -double-negative thymocytes were observed in malnourished rats. In addition, single-positive CD8+ and single-positive CD4 + thymocytes had higher frequencies of apoptosis in malnourished rats. The frequency of total dexamethasone-induced apoptosis was found to be similar in both groups of animals. Nevertheless, in malnourished dexamethasonetreated animals, the percentage of apoptotic double-negative thymocytes was significantly higher than in well-nourished animals, while the rate of apoptosis was lower among double-positive cells. In general, the thymus appears more sensitive to the effects of malnutrition and dexamethasone than the spleen. Furthermore, double-negative thymocytes appear to be the most affected.Keywords: apoptosis, cell death, lymphoid atrophy, malnourished, spleen, thymus

SUMMARYThe aim of this study was to determine if the distribution in vivo of CD4 1 CD45RA 1 /CD45RO 2 (naive), CD4 1 CD45RA 1 /CD45RO 1 (Ddull) and CD4 1 CD45RO 1 (memory) lymphocytes differs in malnourished infected and well-nourished infected children. The expression of CD45RA (naive) and CD45RO (memory) antigens on CD4 1 lymphocytes was analysed by flow cytometry in a prospectively followed cohort of 15 malnourished infected, 12 well-nourished infected and 10 well-nourished uninfected children. Malnourished infected children showed higher fractions of Ddull cells (11´4^0´7%) and lower fractions of memory cells (20´3^1´7%) than the well-nourished infected group (8´8^0´8 and 28´1^1´8%, respectively). Well-nourished infected children showed increased percentages of memory cells, an expected response to infection. Impairment of the transition switch to the CD45 isoforms in malnourished children may explain these findings, and may be one of the mechanisms involved in immunodeficiency in these children.

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SummaryThe mechanisms involved in impaired immunity in malnourished children are not well understood. T cells in MNI children may represent an ineffective response to infection. Levels of effector T cells in children with gastrointestinal infections versus those suffering from respiratory infections were also significantly different within the WNI group. While WNI children with gastrointestinal infections had higher absolute and relative values of CD8+ , and CD8 + CD28 -T subsets, by those with respiratory infections had higher values of CD4 + lymphocytes. However, due to the small number of subjects examined, our results in WNI children should be interpreted with caution and confirmed using a larger sample size. Our data suggest that altered expression of CD62L and CD28 receptors may contribute to impaired T cell function observed in MNI children.

The aim of this study was to assess DNA repair capacity in lymphocytes of children with protein calorie malnutrition using the single-cell gel electrophoresis (comet) assay. Repair capacity was assessed by estimating the relative decrease of DNA migration length 5, 15, 30, and 60 min after hydrogen peroxide treatment, in three groups of children: well-nourished (WN), well-nourished infected (WN-I), and malnourished infected (MN-I). In addition, the DNA migration length was evaluated in all groups before and after peroxide treatment. Comparison of mean migration lengths observed in WN and WN-I children showed significant differences at all times tested; between WN-I and MN-I differences were also observed, except after hydrogen peroxide exposure. This implies that lymphocytes of WN-I and MN-I children were equally sensitive to hydrogen peroxide. Nevertheless, the MN-I group clearly shows the greatest overall percentage of damaged cells at all times tested. In relation to repair capacity, at 5 min it was approximately 30% in both groups of well-nourished children, but only 20% in MN-I; 15 min after exposure, repair capacity increased to 51% in well-nourished children but only to 31% in MN-I; and at 60 min this capacity increased to 82% in well-nourished but only to 55% in MN-I. These data indicate that lymphocytes of malnourished children show a decreased capacity to repair hydrogen peroxide-induced DNA damage compared to that of well-nourished controls. This reflects that only malnutrition is associated with decreased DNA repair capacity. Additionally, the data confirm that severe infection and malnutrition are two factors clearly associated with increased DNA damage.