Moreover, the optimal level of cross-reactivity increases with decreases in repertoire size – i.e., fewer lymphocyte receptors must cross-react more, to cover antigenic space – but that strategy risks autoimmunity (Borghans et al. 1999).
Using improved sensitivity of NGS, we find that in most SLE subjects (nine of eleven), flaring to moderate disease activity level was not associated with an increase in clonal expansion or a decrease in overall repertoire diversity.
No significant correlation between the overall repertoire diversity and clinical disease activity was observed for most SLE patients with only two of eleven SLE patients showing a decreasing trend in repertoire diversity approaching the flare time point.
This observation is supported on a molecular level by previous data showing that CD8+ T cells lose their naïve T cell compartment more rapidly than CD4+ T cells during mid-adulthood and most recently published data confirmed age-related decreases in TCRβ repertoire diversity by HTS (24, 25).
A significant decrease in T cell repertoire diversity was observed in PB of SLE patients compared to HC.
Age-associated alterations in adaptive immune responses are characterized by impaired B and T lymphopoiesis, as well as functional alterations in signaling and a marked decrease in antigen receptor gene repertoire diversity [ 4].
Tumor progression induces rigorous immunosuppression by inducing apoptosis in T cells [ 12- 18, 19] 19] and reducing Th1/Tc1 response [ 20] thereby leading to decrease in activated T cell repertoire [ 15- 17], which includes the abolishment of effective cell-mediated immune response of the host.
The presence of collagen-specific T cells in the peripheral blood was modulated by therapy, and remission of the disease was associated with a decrease in the collagen-specific TCR repertoire, whereas relapses of the disease were accompanied by reappearance of the same T-cell repertoire detected at the onset.
The decrease in the size of the OR gene repertoire in humans and the large number of pseudogenes likely reflect a lessening of evolutionary pressure due to a decrease in human dependence upon olfactory cues for survival.
Nevertheless, there were distinct changes in the Ig-VH repertoire that paralleled the decrease in clinical activity – certain genes were shown to fluctuate, for instance the genes of the VH2 family or the gene VH3 23.
