Differences in Alloimmune Response Between Elderly and Young Mice

Abstract

ObjectiveThe upper age of renal transplant recipients is rising on the transplant wait list. Age-dependent immune responsiveness to new antigens has not been thoroughly studied. This study used a mouse model of alloantibody response to neoalloantigen to study age-related differences. MethodsTransgenic huCD20-C57BL/6 mice were immunized intraperitoneally with BALB/c splenocytes (2.5 × 107) at baseline and 1 month. Plasma samples were collected at baseline and 1 and 2 months after inoculation, frozen, and tested in a batch run (n = 22). Samples were tested by flow cytometric crossmatch for alloantibody with 2-fold serial dilution from neat to 1:640 using BALB/c splenocytes as targets. The sum of the median fluorescence intensity of the tested sample was calculated after subtracting that of an autologous serum control. Elderly mice (ELD; 42–103 weeks) at inoculation were compared with younger mice (YOU; 11–15 weeks). Statistical analysis was performed with 2-sample t test. ResultsMean age (weeks) between the groups was significantly different (ELD 69.3 ± 9.6 vs YOU 13.4 ± 1.4; P < .001). There was no difference in alloantibody between groups at baseline (ELD 0.7 ± 3.1 vs YOU 0.6 ± 0.4; P = .93). There was a higher alloantibody response at 1 month for YOU (52.9 ± 31.78) compared with ELD (5.12 ± 8.18). There was a greater difference after the 2 month (YOU 109.38 ± 66.43 vs ELD 21.97 ± 27.14; P < .0024). ConclusionsThere was a difference in response to new alloantigen in this animal model. Older animals had significantly decreased responses to new alloantigen stimulation 1 month after inoculation and even more profound decreases at 2 months compared with young animals. This model may be used to study differences in immune refractoriness to antigen signaling. It may be important to adapt clinical immunosuppression in the aged population to possible decreased responses to immune stimulation.