Role of antigen‐presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages

Abstract

Immune challenges can elicit polarized responses skewed towards the development of T helper type 1 (Th1) or Th2 T cell subsets. To determine if distinct antigen-presenting cells (APC) populations might selectively influence Th subset development, we studied the role of two key APC populations, B cells and macrophages, in the differentiation of effector Th populations from naive precursor Th in vitro. Antigen (Ag)-specific, naive CD4+ T cells were enriched from a mouse strain, AND, bearing a transgenic alpha/beta T cell receptor (TCR) encoding reactivity with pigeon cytochrome c peptide 88-104. Peptide Ag was used throughout these studies so that differences in the uptake and processing by the two APC populations would not influence the results. Both APC populations, activated B cells and bone marrow-derived macrophages, supported the development of effector Th having the capacity to secrete high levels of cytokines when restimulated. Regardless of APC population present during effector development, exogenous interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) had dominant effects on Th subset development. Thus, with both APC populations, effector Th generated in the presence of IFN-gamma acquired a Th1-type cytokine profile, Th generated with IL-4 acquired a Th2-type cytokine profile, and Th generated without IFN-gamma or IL-4 acquired a Th0-type cytokine profile. B cells and macrophages also had equivalent APC function in the restimulation of Th1 and Th2-like effectors, since only minor differences in cytokine production were noted for these effector populations when restimulated with the two APC populations. However, in 8 of 19 experiments, the Th0-like effector population generated in the presence of IL-2 differentially responded to restimulation with B cells and macrophages, secreting significantly more IFN-gamma when restimulated with B cells, and significantly more IL-4 when restimulated with macrophages. We also found that Th effector populations recultured in IFN-gamma or IL-4 assumed a more Th1 or Th2-like phenotype, respectively, regardless of their initial cytokine profile. We conclude that through a subtle capacity to skew cytokine production by a Th0 subset, different APC may selectively influence Th subset development under conditions of prolonged or chronic stimulation in an autocrine fashion.

Increase of tuberculous infection in the organs of B cell-deficient mice

“…Second, B cells can bias the phenotype of T cell responses toward a Th2 profile [11,23,24] [25]). However, we found the IFN-response to mycobacterial antigens unimpaired.…”

Both Dendritic Cells and Macrophages Can Stimulate Naive CD8 T Cells In Vivo to Proliferate, Develop Effector Function, and Differentiate into Memory Cells

“…In addition, our experiments using T cells as APCs demonstrate that the ability of an Ag-bearing cell to migrate into the lymph nodes is not a sufficient property to initiate responses. It is possible that B cells can prime T cell responses in vivo, although this has been controversial (77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88). How do M⌽ compare with DCs in stimulating T cell responses?…”

No evidence for involvement of IL-4R and CD11B from the IBD1 region and STAT6 in the IBD2 region in Crohn's disease

“…The interleukin-4 receptor (IL-4R) gene forms an excellent candidate due to its location, the gene coincides with a strong linkage peak in IBD1 (Figure 1), and its function in a signaling pathway leading to T-cell differentiation, which is important in inflammatory responses. 4,5 Another putative candidate in IBD1 is the gene encoding complement receptor type 3 (CD11B). CD11B is a leukocyte surface antigen involved in granulocyte cell adhesion and is upregulated in patients with IBD.…”