Biomedical subjects

Bengt Johansson-Lindbom

Publications and source records attributed to Bengt Johansson-Lindbom.

4 recordsLinked to original sources

PubMed2003

Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT): requirement for GALT dendritic cells and adjuvant.

In the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the chemokine receptor CCR9 and integrin alpha4beta7 by activated CD8+ T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8+ T cell transfer model, antigen-specific T cells entering the small intestinal epithelium were homogeneously CCR9+alpha4beta7+CD62Llow, and this phenotype was only generated in GALT and in the presence of adjuvant. Consistent with the CCR9+ phenotype of the gut-homing T cells, CCR9 was found to play a critical role in the localization of T cells to the small intestinal epithelium. Together, these results demonstrate that GALT DCs and T cell expression of CCR9 play critical and integrated roles during T cell homing to the gut.

Adjuvants, Immunologic↗

PubMed2003

Germinal centers regulate human Th2 development.

In the present study we demonstrate that all CD4(+) T cells in human tonsil expressing the Th2-selective receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) also 1) express high levels of CXCR5, and 2) display a transitional CD45RA/RO phenotype and consistently do not produce significant amounts of cytokines when immediately analyzed ex vivo. Hence, they represent precursors of Th2 effector cells, a conclusion confirmed by their robust production of IL-4, IL-5, and IL-13, but not IFN-gamma, after in vitro activation. CD4(+) T cells, which express only intermediate levels of CXCR5, instead develop into IFN-gamma-producing cells under identical culture conditions, thus establishing a correlation between relative levels of CXCR5 expression and the acquired cytokine profile. Because CXCR5 is critically involved in follicular localization, the results suggest that these CRTH2(+) Th2 cells preferentially develop their cytokine-producing phenotype within germinal centers (GCs), whereas extrafollicular differentiation instead promotes Th1 development. In support for this proposal, we show that T cells with an intermediate expression of CXCR5 can be forced to also produce IL-4 and IL-13 if cultured with allogenic GC B cells. Finally, we demonstrate that the previously described CD57(+) GC T cells also express high levels of CXCR5 but instead of comprising a Th2 precursor, they represent anergized T cells. Taken together, these data suggest that GCs and B cells regulate CD4(+) T cell differentiation in a finely tuned fashion, either by promoting differentiation of Th2 cells, which apparently leave the lymphoid tissue before evolving a cytokine-producing phenotype, or by furnishing T cell unresponsiveness.

B-Lymphocyte Subsets↗

PubMed2002

Germinal center B cells constitute a predominant physiological source of IL-4: implication for Th2 development in vivo.

Protective immunity depends upon the capability of the immune system to properly adapt the response to the nature of an infectious agent. CD4(+) Th cells are implicated in this orchestration by secreting a polarized pattern of cytokines. Although Th2 development in animal models and in human cells in vitro to a large extent depends on IL-4, the nature of the cells that provide the initial IL-4 in vivo is still elusive. In this report, we describe the anatomical localization as well as the identity of IL-4-producing cells in human tonsil, a representative secondary lymphoid organ. We demonstrate that IL-4 production is a normal and intrinsic feature of germinal center (GC) B cells. We also show that expression of IL-4 is highly confined to the GCs, in which the B cells constitute the prevalent cellular source. Furthermore, immunofluorescence analysis of colon mucosa reveals a strikingly similar pattern of IL-4-expressing cells compared with tonsils, demonstrating that IL-4 production from GC B cells is not a unique feature of the upper respiratory tract. Our results show that GCs provide the most appropriate microenvironment for IL-4-dependent Th2 polarization in vivo and imply a critical role for GC B cells in this differentiation process.

B-Lymphocyte Subsets↗

PubMed2002

Global reprogramming of dendritic cells in response to a concerted action of inflammatory mediators.

Maturation of dendritic cells (DC) serves a deterministic role in the link between innate and adaptive immunity, constituting a checkpoint with regard to whether responses from the lymphocyte compartment shall be raised and what class of response is needed to protect the host against invading pathogens. Since DC have not been shown to possess mechanisms such as gene recombination or somatic mutation for generating a diverse repertoire of antigen-recognition receptors, it is unlikely that these leukocytes can intrinsically respond to all conceivable molecules present in our environment. In the present study, we have therefore determined how mediators of the inflammatory response regulate global gene transcription in DC. The data represent an extensive and time-ordered reprogramming of the DC during their course of maturation, involving genes encoding proteins that regulate responses of both innate cells and lymphocytes. This transcriptional reorganization may reflect the effect of in vivo released inflammatory mediators induced by endogenous or pathogenic stimulation.

Antigens, CD↗