Overabundance of CD45RA+ (Quiescent-Phenotype) Cells within the Involuted CD4+ T-Cell Population Follows Initiation of Immune Depression in Energy-Deficient Weanling Mice and Reflects Involution Exclusive to the CD45RA− Subset

Abstract

Previous studies have identified an overabundance of quiescent-phenotype (CD45RA(+)) CD4(+) T cells throughout the lymphoid system of weanling mice at an advanced stage of food intake restriction mimicking marasmus. The objective of this investigation was to determine the timing of this phenomenon relative to the development of depression in cell-mediated immune competence. Two experiments were conducted in which male and female weanling C57BL/6J mice, initially 19 d of age, either were permitted free access to a complete purified diet or were subjected to restricted intake of this diet, producing loss of 1.5-2% of initial body weight daily. In the first experiment, feeding periods of 3, 6, 9, 12 and 14 d were examined, and a zero-time control group (19 d old) was also included. Expression of CD45RA was assessed by flow cytometry in CD4(+) T cells from the blood, spleen and mesenteric lymph nodes. Despite reduction in CD4(+) T-cell numbers, evident in all three lymphoid compartments of the malnourished mice by d 6, energy-restricted mice maintained the numbers of CD4(+)CD45RA(+) T cells at the level found in the zero-time control group. Consequently, the malnourished group exhibited a high percentage of CD4(+) T cells expressing CD45RA by d 9 in the blood and mesenteric nodes and by d 12 in the spleen. In the second study, malnourished and age-matched control groups were sensitized to sheep red blood cells on d 3 and energy-restricted mice exhibited depression in the delayed hypersensitivity response to this antigen when assessed on d 9 after challenge 24 h previously. Energy deficiency pathology includes a shift toward CD4(+) T cell quiescence that may contribute to ongoing immunodepression without being involved in its initiation. Remarkably, this imbalance develops because involution of the CD4(+) subset in the energy-deficient mice is confined to the CD45RA(-) population.

Adoptively Transferred Dendritic Cells Restore Primary Cell-Mediated Inflammatory Competence to Acutely Malnourished Weanling Mice

“…The food intakes and gains in fat and lean tissue exhibited by the age-matched control groups were comparable with previous results pertaining to C57BL/6J weanlings given free access to the same complete purified diet. 6,13 By contrast, consumption of the low-protein diet induced decrements of both fat and lean tissue with resultant daily weight loss of approximately 1.7% of initial body weight. Furthermore, the protein-deficient diet produced low food intakes relative to the complete diet, including low levels of intake on a body weight basis.…”

“…Caging and housing conditions were as described previously, 6,13,14 and the investigation was approved by the Animal Care Committee of the University of Guelph in accordance with the Canadian Council on Animal Care.…”

“…Single-cell suspensions of mononuclear cells were prepared as described previously 6 from the mesenteric, inguinal, and submandibular lymph nodes of C57BL/6J mice at 4 to 6 months of age. The cells were suspended in RPMI 1640 (Sigma Chemical) supplemented with 100 ml/L heat-inactivated fetal bovine serum (Sigma Chemical), 1 mmol/L HEPES (ICN Biomedicals), 10 5 U/L penicillin, and 100 mg/L streptomycin (complete medium).…”

“…Generic aspects of staining procedures in this laboratory were described previously. 6 Each analysis was based on at least 10 4 events after dead cells and residual erythrocytes were eliminated by gating on the basis of forwardangle light scatter.…”

“…2 Lymphoid atrophy is characteristic of acute deficits of nitrogen and energy and is legitimately regarded as an important contributor to the associated immune depression. Moreover, within the involuted Tlymphocyte system, an overabundance of the relatively quiescent naïve type of T cell is apparent phenotypically in acutely malnourished children 5 and rodents, 6 and this observation has been extended more recently by studies of polyclonal T-cell activation in vitro. 7 The foregoing evidence of a naïve-shift within the T-cell compartment focuses attention on the dendritic cell because of its unique role as the antigen-presenting cell for the naïve T cell, ie, for initiating primary T-dependent immune responses.…”