In Vivo–Activated Cd4 T Cells Upregulate Cxc Chemokine Receptor 5 and Reprogram Their Response to Lymphoid Chemokines

Abstract

Migration of antigen-activated CD4 T cells to B cell areas of lymphoid tissues is important for mounting T cell–dependent antibody responses. Here we show that CXC chemokine receptor (CXCR)5, the receptor for B lymphocyte chemoattractant (BLC), is upregulated on antigen-specific CD4 T cells in vivo when animals are immunized under conditions that promote T cell migration to follicles. In situ hybridization of secondary follicles for BLC showed high expression in mantle zones and low expression in germinal centers. When tested directly ex vivo, CXCR5hi T cells exhibited a vigorous chemotactic response to BLC. At the same time, the CXCR5hi cells showed reduced responsiveness to the T zone chemokines, Epstein-Barr virus–induced molecule 1 (EBI-1) ligand chemokine (ELC) and secondary lymphoid tissue chemokine (SLC). After adoptive transfer, CXCR5hi CD4 T cells did not migrate to follicles, indicating that additional changes may occur after immunization that help direct T cells to follicles. To further explore whether T cells could acquire an intrinsic ability to migrate to follicles, CD4−CD8− double negative (DN) T cells from MRL-lpr mice were studied. These T cells normally accumulate within follicles of MRL-lpr mice. Upon transfer to wild-type recipients, DN T cells migrated to follicle proximal regions in all secondary lymphoid tissues. Taken together, our findings indicate that reprogramming of responsiveness to constitutively expressed lymphoid tissue chemokines plays an important role in T cell migration to the B cell compartment of lymphoid tissues.

B cells alter the phenotype and function of follicular‐homing CXCR5+ T cells

“…Of note, successful B cell responses to Tdependent antigens require that both cellular partners be in a state of "priming". This cellular co-localization correlates well with induction of CXCR5 expression on T cells and modulation of B cell responses to LN chemokines [12,13]. In humans, in vitro stimulation of naive CD4 + T cells results in the rapid and uniform induction of CXCR5 expression [14], suggesting that, similar to the situation in mice, priming of T cells in the T cell zone of human secondary lymphoid tissues also results in their relocation toward the B cell compartment.…”

Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells

“…After immunization with soluble protein antigens, rapid expansion of antigen-specific cells in the T zone is accompanied by their selective migration to B follicles, and this coincides with the in vivo expression of CXCR-5 13. This chemokine receptor is responsible for localizing lymphocytes in B follicles 14, where the ligand is expressed 15.…”

Expression Profiling of Murine Double-Negative Regulatory T Cells Suggest Mechanisms for Prolonged Cardiac Allograft Survival

“…CXCR5 was described initially in Burkitt's lymphoma as a G protein-coupled receptor (45) and subsequently found in B cells and a subset of CD4 ϩ T cells (46). More recently, CXCR5 expression has also been shown in DN T cells from MRL-Lpr mice (47). CXCR5 responds to its exclusive ligand CXCL13 by initiating chemotaxis toward an increasing gradient in vitro and to B cell zones in lymph nodes that express CXCL13 (47)(48)(49).…”