Flexible Programs of Chemokine Receptor Expression on Human Polarized T Helper 1 and 2 Lymphocytes

TLDR

Let's parse. Background: "Chemokines and their receptors are important elements for the selective attraction of various subsets of leukocytes." Purpose+Mechanism: "To better understand the selective migration of functional subsets of T cells, chemokine receptor expression was analyzed using monoclonal antibodies, RNase protection assays, and the response to distinct chemokines." This sentence covers both purpose and mechanism. Findings: combine all findings into one sentence summarizing main results: naive T cells express only CXCR4; memory/activated express CXCR3; Th0/Th1 high CXCR3, Th2 low; CCR3/CCR4 on Th2; functional responses accordingly; CCR5 expression variable; cytokines influence expression; TGF-beta and IFN-alpha modulate receptors; overall receptors are markers of naive/polarized subsets and flexible programs may control migration. Let's craft: "Naïve T cells express only CXCR4, whereas memory/activated cells predominantly express CXCR3, with Th0/Th1 showing high CXCR3 and Th2 low; Th2 cells uniquely express CCR3 and CCR4 and respond to their agonists, while Th0/Th1 respond to CXCR3 agonists; CCR5 expression varies with IL‑2, and cytokines such as TGF‑β and IFN‑α modulate receptor patterns, demonstrating that chemokine receptor profiles mark naive and polarized T‑cell subsets and may govern tissue‑specific migration." Check length: It's long but still one sentence.

Abstract

Chemokines and their receptors are important elements for the selective attraction of various subsets of leukocytes. To better understand the selective migration of functional subsets of T cells, chemokine receptor expression was analyzed using monoclonal antibodies, RNase protection assays, and the response to distinct chemokines. Naive T cells expressed only CXC chemokine receptor (CXCR)4, whereas the majority of memory/activated T cells expressed CXCR3, and a small proportion expressed CC chemokine receptor (CCR)3 and CCR5. When polarized T cell lines were analyzed, CXCR3 was found to be expressed at high levels on T helper cell (Th)0s and Th1s and at low levels on Th2s. In contrast, CCR3 and CCR4 were found on Th2s. This was confirmed by functional responses: only Th2s responded with an increase in [Ca2+]i to the CCR3 and CCR4 agonists eotaxin and thymus and activation regulated chemokine (TARC), whereas only Th0s and Th1s responded to low concentrations of the CXCR3 agonists IFN-γ–inducible protein 10 (IP-10) and monokine induced by IFN-γ (Mig). Although CCR5 was expressed on both Th1 and Th2 lines, it was absent in several Th2 clones and its expression was markedly influenced by interleukin 2. Chemokine receptor expression and association with Th1 and Th2 phenotypes was affected by other cytokines present during polarization. Transforming growth factor β inhibited CCR3, but enhanced CCR4 and CCR7 expression, whereas interferon α inhibited CCR3 but upregulated CXCR3 and CCR1. These results demonstrate that chemokine receptors are markers of naive and polarized T cell subsets and suggest that flexible programs of chemokine receptor gene expression may control tissue-specific migration of effector T cells.