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

Previous studies have identified an overabundance of quiescent-phenotype (C D45RA(+)) CD4(+) T cells throughout the lymphoid system of weanling mice at an advanced stage of food intake restriction mimicking marasmus. The objec tive of this investigation was to determine the timing of this phenomenon r elative 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 comple te purified diet or were subjected to restricted intake of this diet, produ cing 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 cont rol group (19 d old) was also included. Expression of CD45RA was assessed b y flow cytometry in CD4(+) T cells from the blood, spleen and mesenteric ly mph nodes. Despite reduction in CD4(+) T-cell numbers, evident in all three lymphoid compartments of the malnourished mice by d 6, energy-restricted m ice maintained the numbers of CD4(+)CD45RA(+) T cells at the level found in the zero-time control group. Consequently, the malnourished group exhibite d 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, malno urished and age-matched control groups were sensitized to sheep red blood c ells on d 3 and energy-restricted mice exhibited depression in the delayed hypersensitivity response to this antigen when assessed on d 9 after challe nge 24 h previously. Energy deficiency pathology includes a shift toward CD 4(+) T cell quiescence that may contribute to ongoing immunodepression with out being involved in its initiation. Remarkably, this imbalance develops b ecause involution of the CD4(+) subset in the energy-deficient mice is conf ined to the CD45RA(-) population.