Naïve helper T cells with high CD5 expression have increased calcium signaling

Abstract

The adaptive immune response is orchestrated by T helper cells and their function is dependent upon interactions between the T cell receptor (TCR), peptide MHC (pMHC) and co-receptors. TCR-pMHC interactions initiate calcium signaling cascades which determine T cell activation, survival, proliferation and differentiation. CD5 is a co-receptor that plays an important role in regulating T cell signaling and fate during thymocyte education. CD5 surface expression on mature single positive thymocytes correlates with the TCR signal strength for positive selecting self-ligands. CD5 also plays a role in T cell function after thymic development is complete. Peripheral T cells with higher CD5 expression respond better to foreign antigen than those with lower CD5 expression and CD5-high T cells are enriched in memory populations. In our study, we examined the role of CD5 expression and calcium signaling in the primary response of T cells using two Listeria monocytogenes specific T helper cells (LLO118 and LLO56). These T cells recognize the same immunodominant epitope (LLO190-205) of L. monocytogenes and have divergent primary and secondary responses and different levels of CD5 expression. We found that each T cell has unique calcium mobilization in response to in vitro stimulation with LLO190-205 and that CD5 expression levels in these cells changed over time following stimulation. LLO56 naïve T helper cells, which expresses higher levels of CD5, have higher calcium mobilization than naïve LLO118 T cells. Three days after in vitro stimulation, LLO118 T cells had more robust calcium mobilization than LLO56 and there were no differences in calcium mobilization 8 days after in vitro stimulation. To further evaluate the role of CD5, we measured calcium signaling in CD5 knockout LLO118 and LLO56 T cells at these three time points and found that CD5 plays a significant role in promoting the calcium signaling of naïve CD5-high LLO56 T cells.

Whole-Genome Methylation Analysis Reveals Epigenetic Variation in Cloned and Donor Pigs

“…Found in T lymphocytes, CD5 is a type of cluster differentiation antigen. High CD5 expression in peripheral T cells allows them to better respond to foreign antigens and enrich memory populations to produce stronger antigenic responses when exposed to the same antigen again (Freitas et al, 2017). Differences in CD5 methylation may lead to a change in the expression of CD5 in the peripheral blood of the CP and DP in this study, which may have had an effect on the immune responses of the two pigs during immunization programs.…”

Differential interferon‐gamma production potential among naïve CD4+ T cells exists prior to antigen encounter

“…In addition, differences in IFNγ production remain evident in activated monoclonal CD5 lo versus CD5 hi CD4 + T cells in response to antigen challenge in vivo . TCR affinity for foreign antigen alone, however, is not the only factor influencing TCR signal strength, and it has previously been shown that the kinetics of cytosolic calcium mobilization in CD5 lo and CD5 hi CD4 + T cells after activation is distinct even when TCR affinity for cognate antigen is identical between the two populations . More recently, it has been suggested that strong basal TCR signals correlate with higher expression of negative regulators of TCR signaling as well as markers of anergy and are associated with attenuated responses to agonist stimulation .…”

“…TCR affinity for foreign antigen alone, however, is not the only factor influencing TCR signal strength, and it has previously been shown that the kinetics of cytosolic calcium mobilization in CD5 lo and CD5 hi CD4 + T cells after activation is distinct even when TCR affinity for cognate antigen is identical between the two populations. 28 More recently, it has been suggested that strong basal TCR signals correlate with higher expression of negative regulators of TCR signaling as well as markers of anergy and are associated with attenuated responses to agonist stimulation. 26 Thus, in addition to evidence of cytokine production modulation by CD5 itself, 13,18 there is likely a complex interplay of distinct affinities for foreign antigen, TCR signal modulation, metabolic profiles and cytokine sensitivity, that drive differences in IFNc production potential in CD5 lo and CD5 hi CD4 + T-cell subsets.…”

The multiple faces of CD5

“…Moreover, CD5 appeared to play an important role in this Ca 2+ mobilization, as the LL056 CD5-deficient T cells showed reduced Ca 2+ responses compared to CD5 sufficient ones. 89 naïve thymocytes from CD5-deficient mice showed enhanced cell death, which correlated with reduced levels of pAKT after stimulation with anti-CD3 + anti-CD28. 62 It has been reported that the PI3K/AKT/mTOR pathway inhibits Tregs generation, and therefore it is possible that the decreased Akt phosphorylation might favor tTreg generation in CD5-deficient mice.…”

“…The enhanced T cell response of LL056 T cells correlated with an increased calcium mobilization at early times after stimulation compared to that observed in LLO118 cells. Moreover, CD5 appeared to play an important role in this Ca 2+ mobilization, as the LL056 CD5‐deficient T cells showed reduced Ca 2+ responses compared to CD5 sufficient ones …”