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.