Abstract
Memory T and B lymphocyte numbers are thought to be regulated by recent and cumulative microbial exposures. We report here that memory-phenotype lymphocyte frequencies in B, CD4 and CD8 T-cells in 3-monthly serial bleeds from healthy young adult humans were relatively stable over a 1-year period, while Plasmablast frequencies were not, suggesting that recent environmental exposures affected steady state levels of recently activated but not of memory lymphocyte subsets. Frequencies of memory B and CD4 T cells were not correlated, suggesting that variation in them was unlikely to be determined by cumulative antigenic exposures. Immunophenotyping of adult siblings showed high concordance in memory, but not of recently activated lymphocyte subsets. To explore the possibility of cell-intrinsic regulation of T cell memory, we screened effector memory-phenotype T cell (TEM) frequencies in common independent inbred mice strains. Using two pairs from these strains that differed predominantly in either CD4 TEM and/or CD8 TEM frequencies, we constructed bi-parental bone marrow chimeras in F1 recipient mice, and found that memory T cell frequencies in recipient mice were determined by donor genotypes. Together, these data suggest cell-autonomous determination of memory T niche size, and suggest mechanisms maintaining immune variability.
Highlights
Gene-environment interplay in immune phenotypes has been extensively studied using steady-state cellular immune profiles [1,2,3], functional immune responses [2,4,5,6,7,8], post-vaccination responses [9,10] and V,D and J usage biases in naïve and memory T and B cell compartments [11]
Gating strategy for the memory subsets is indicated in S1 Fig. For cell subset frequencies the following parameters were quantified: Naive B cells, memory B cells and plasmablasts, naive CD4 and memory CD4, and naive CD8, memory CD8 and CD8 TEMRA
The analysis showed that differences in cell frequencies between siblings were significantly less than the differences between random pairs of non-siblings for memory CD4, memory CD8 and memory B cells, but not for plasmablasts and CD8 TEMRA cell frequencies (Fig 3 and S2 Table), suggesting that the memory and naive B, CD4 and CD8 subsets could be determined by shared early developmental environmental factors or hereditary factors
Summary
Gene-environment interplay in immune phenotypes has been extensively studied using steady-state cellular immune profiles [1,2,3], functional immune responses [2,4,5,6,7,8], post-vaccination responses [9,10] and V,D and J usage biases in naïve and memory T and B cell compartments [11]. Some of these studies have identified genomic correlates associated with specific steady-state immune phenotypes [2] and vaccine responses [12]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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