No abstract

SummaryPrevious studies have demonstrated metabolic dysfunction in the mononuclear cells of some children with abnormal cell-mediated immunity. Interpretation of these observations has been complicated by the extreme heterogeneity of cell types examined. The glycolytic metabolism of relatively enriched T-cells, non-T mononuclear cells (NTM), non-T lymphocytes (NTL), and monocytes was studied in an attempt to measure the metabolism of subpopulations of mononuclear cells.Lactate production by monocytes was 11 times greater than that of T-cells and 2% times greater than that of non-T lymphocytes. Exposure to phytohemagglutinin (PHA) stimulated glycolytic metabolism in T-cells but did not stimulate glucose utilization or lactate production in NTM. Even when T-cells were maximally stimulated by PHA, their observed metabolism was still lower than that of NTL. The ATP content of T lymphocytes and NTL was similar and was constant under the conditions of incubation. The initial ATP content of monocytes was higher than that of lymphocytes, and diminished during incubation.Tricarboxylic acid cycle activity did not contribute significantly to ATP synthesis in any of the mononuclear cell subpopulations, under the conditions of incubation used in this study. Significant hexose monophosphate shunt activity was observed in all mononuclear cell types.These studies demonstrate major metabolic differences between mononuclear cell subtypes. Any correlation of metabolic observation with clinical dysfunction of mononuclear cells requires the study of relatively pure cell populations. SpeculationThe reason for increased glycolysis in NTL is obscure. It may imply an immaturity of a portion of those cells, by analogy to the increased glycolytic activity of young erythrocytes. Alternatively, a subset of NTL may require increased ATP synthesis to perform its functions. In order to delineate these possibilities, methods must be developed which will allow the isolation of large numbers of B and Null lymphocytes for metabolic and functional studies.The performance of biologic functions by cells requires the expenditure of energy derived from cellular metabolism. Cellular dysfunction can be correlated with perturbations of energy metabolism by the dysfunctional cell. This correlation has been most strikingly demonstrated in erythrocytes, in which a variety of hemolytic anemias have been correlated with inherited disorders of glycolysis (17). More recent data suggest that the defect in platelets of patients with Wiskott-Aldrich Syndrome may be related to an inborn error of the Krebs Cycle (14).The authors postulated that malfunction of human mononuclear leukocytes might be caused by or associated with disorders of energy metabolism. Several models of cell-mediated immune dysfunction were studied and diminished ATP content in the mononuclear cells of newborn infants (5) and patients with severe malnutrition (4) have been described. Spec*c correlation between a metabolic deficit and a cellular malfunction could not be made because of the heterog...

Pulmonary infection with Pseudomonas aeruginosa (PA)eventually occurs in virtually every patient with cystic fibrosia. Progression of infection and, ultimately, death occurs despite circulating specific antibody. For these reasons, studies of cell mediaeed imune responses to PA were undertaken in patients with cystic fibrosis. In vitro lymphocyte proliferative responses to PA, Hemophilus influenzae, Streptococcus hemolyticus and Staphylococcus aureus antigen were tested by ' H thymidine incorporation. --Twenty-nine patients with chronic PA infection including 16 in fair or good condition (Shwachman Case Hiatory Score of 15-25 points) and 13 in poor condition (Score of 1-14) were tested. In addition, 6 patients who had never had PA recovered from sputum cultures and 13 normal persons were also tested. The mean response to three different PA strains was 753 counts per minute (cpm) in the "poor" group compared to 3234 cpm in the "good" group (pq0.0005) and 2572 in the normal groups (~~0.005). This difference was not present in the responses to PHA and Con-A or to the other bacterial antigens. Two terminally ill patients gave lower responses to four of their own PA strains than did the other patients. In addition, two sibling pairs in which onechild waa aeverely ill and infected with PA while the other child had not yet shown PA on sputum cultures were studied. In both cases, the uninfected child had normal responses, whereaae the severely ill siblinghadvirtually no response against his own PA. The addition of PHA to T-cell incubation caused an immediate four-fold stimulation of GU while non-T cells were totally unaffected (92+22 vs 196+20).Lactate production (LP) by enriched T-cells (s219) was k c h less than LP by non-T cells (351535) (p