Cell Subpopulations In Lymph Nodes Research Articles

PPARα regulates endothelial progenitor cell maturation and myeloid lineage differentiation through a NADPH oxidase-dependent mechanism in mice.

Peroxisome proliferator-activated receptor-alpha (PPARα) is a key modulator of lipid metabolism. Here, we propose that PPARα regulates the maturation and function of bone marrow (BM) progenitor cells. Although PPARα deletion increased the number of BM-resident cells and the differentiation of endothelial progenitor cells (EPCs) and monocytic progenitor cells, it impaired re-endothelialization of injured carotid artery that was associated with reduced circulating EPCs. Also, PPARα deletion diminished the in vivo proangiogenic effect of PPARα agonist without affecting EPC differentiation markers. Macrophage colony-stimulating factor treatment increased the population of monocytic progenitor cells as well as secretome of BM-derived cells in PPARα wild-type but not in knockout mice. In addition, PPARα-null mice displayed reduced lymphocytes and increased monocytes and neutrophils in the blood. Furthermore, PPARα-null mice exhibited increments in the number of total cells (as well as of phenotypically distinct subpopulations of lymph node cells) but also a significant alteration in the number of various subpopulations of splenocytes and thymocytes. Finally, PPARα negatively regulated reactive oxygen species derived by NADPH oxidase in BM-resident progenitor cells. Taken together, our data provide evidence that PPARα is a critical regulator of recruitment, homing, and maturation of BM-derived progenitor cells.

T cell subpopulations in lymph nodes may not be predictive of patient outcome in colorectal cancer

BackgroundThe immune response has been proposed to be an important factor in determining patient outcome in colorectal cancer (CRC). Previous studies have concentrated on characterizing T cell populations in the primary tumour where T cells with regulatory effect (Foxp3+ Tregs) have been identified as both enhancing and diminishing anti-tumour immune responses. No previous studies have characterized the T cell response in the regional lymph nodes in CRC.MethodsImmunohistochemistry was used to analyse CD4, CD8 or Foxp3+ T cell populations in the regional lymph nodes of patients with stage II CRC (n = 31), with (n = 13) or without (n = 18) cancer recurrence after 5 years of follow up, to determine if the priming environment for anti-tumour immunity was associated with clinical outcome.ResultsThe proportions of CD4, CD8 or Foxp3+ cells in the lymph nodes varied widely between and within patients, and there was no association between T cell populations and cancer recurrence or other clinicopathological characteristics.ConclusionsThese data indicate that frequency of these T cell subsets in lymph nodes may not be a useful tool for predicting patient outcome.

The cellular basis of allograft rejection in vivo. III. Restoration of first-set rejection of heart grafts by T helper cells in irradiated rats.

An adoptive transfer model was used to examine the subpopulations of lymphocytes required to effect first-set rejection of directly vascularized heart allografts. PVG heart grafts are not rejected in irradiated DA hosts for at least 50 days. The adoptive transfer of 5 X 10(7) syngeneic lymph node cells (LNC) restores rejection to 14.4 +/- 2.4 days (mean +/- SD). Subpopulations of LNC, were separated by an indirect "panning" technique using the mouse antirat monoclonal antibodies W3/13, MRC OX8, or W3/25 to deplete the unwanted subsets of cells. Each subpopulation was tested, in a number equivalent to the number present in 5 X 10(7) normal LNC, for its ability to cause the rejection of heart grafts. Whole T cells (W3/13+) or helper/inducer T cells (W3/25+) restored graft rejection to 16.4 +/- 3.8 d and 16.0 +/- 2.4 days, respectively. Neither cytotoxic/suppressor T cells (MRC OX8+) nor B cells (Ig+) restored rejection. Indirect immunoperoxidase stains of the grafts showed that although W3/25+ cells predominated in the rejected tissue, MRC OX8+ cells were also present even in grafts from rats restored with inocula that contained less than 1% MRC OX8+ cells. Examination of lymphoid tissues suggested that the MRC OX8+ cells might be of host origin. By the time the grafts were rejected in irradiated hosts, significant thymic regeneration had occurred and there were large numbers of MRC OX8+ cells present in the thymus, as well as some in lymph nodes and spleen.

H 9/25 monoclonal antibody recognizes a new allospecificity of mouse lymphocyte subpopulations: strain and tissue distribution.

C3 H/He-mg mice were immunized with C57BL/10 (B10) spleen cells and the immune spleen cells were fused with BALB/c myeloma cells (NS1). One of the monoclonal antibodies (H9/25 antibody) produced by the hybrid cells was studied. It reacts with subpopulations of B10 lymphocytes as well as some lymphoid tumor lines including some of the Abelson virus-induced leukemias. The antigen recognized by H9/25 antibody is expressed on lymphocytes from all the B10 congeneic mice tested as well as some other strains of mice. No linkage between genes coding for the antigen and H-2 loci was found as judged by its presence on cells of the B10 strains regardless of H-2 type and the distribution of the antigen on Bailey recombinant inbred mice. The antigen is expressed on subpopulations of lymph node cells, spleen cells, thymocytes and bone marrow cells. The strain distribution of the H9/25 antigen seems to be identical to that of Ly-6, Ly-8 and Ala-1 antigens. However, the tissue distribution of the antigen recognized by H9/25 antibody, while similar to these alloantigens, is unique and the antigen may be distinct from the other alloantigens.

In vivo studies on suppressor lymphocyte activity following administration of Escherichia coli O138 lipopolysaccharide

Evaluation of Escherichia coli vaccines used in veterinary practice usually relates to antibody formation and neglects the essential characteristics of cell function leading to this end. This paper attempts to investigate the cellular responses to E coli O138 lipopolysaccharide (LPS) administered subcutaneously in a dose range of 1 microgram to 200 microgram. Rosette-forming cell responses in the draining lymph node varied from antigenic at 10 microgram to tolerogenic at 200 microgram. The tolerogenic dose also caused a marked mitogenic response as can be seen by a fourfold increase in total lymph node cells. Fractionation of normal or LPS-responding, or LPS-tolerised lymph node cells into B cell-rich and T cell-rich fractions was carried out and these were adoptively transferred simultaneously with an antigenic dose of sheep erythrocytes (SRBC) into syngeneic recipient mice. Suppressor activity of the anti-SRBC response was found after transfer of 1 X 10(6) normal B cell fractions, 1 X 10(6) tolerised B cell fractions and 1 X 10(6) tolerised T cell fractions. LPS-antigenically stimulated lymph node cell fractions had no suppressor effect but when given with Freund's complete adjuvant ensuing T cell-rich fractions produced immunosuppression in recipient mice. The significance of these findings is discussed in relation to polyclonal B cell activation, helper and suppressor T cells, and possible feedback mechanisms between interacting subpopulations of lymph node cells.

In vitro sensitization to transplantation antigens : V. Suppression of T-cell and of B-cell function in vitro

A previous report from this laboratory indicated that thymus-bone marrow cooperation occurs during the in vitro sensitization to transplantation antigens. The present report continues our investigation of this T and B cell interaction by attempting to control each of these cell populations in vitro. Two lines of evidence indicate that the T cell is required during the in vitro sensitization to alloantigens: (1) Anti-theta serum pretreatment of lymphoid cells interferes with their ability to become sensitized in vitro to transplantation antigens; (2) Lymphoid cells from neonatally thymectomized donors do not become allosensitized in vitro. In vitro suppression of B cell function was accomplished with an antibone marrow serum (anti-beta serum). Anti-beta serum treatment of lymph node or bone marrow cells impairs the ability of such cells to partcipate in the in vitro sensitization to transplantation antigens. The active cell subpopulations of lymph node cells, obtained by density gradient fractionation, can likewise be suppressed in vitro by pretreatment with anti-theta or anti-beta serum. These results confirm the necessity for thymus-marrow cooperation in vitro, and in addition suggest the existence, in the lymph node, of subclasses of T and B cells participating in the in vitro allograft reaction.

In vitro sensitization to transplantation antigens : IV. Density gradient centrifugation of sensitized cells and sensitization of density gradient-fractionated cells

C57 lymphoid cells were separated, by density centrifugation, into sub-populations of cells. The ability of these subpopulations to become sensitized in vitro to C3H alloantigens was studied. Of the five subpopulations of C57 lymph node, obtained after density gradient centrifugation, only the top, light density (A) and the middle, medium density (C) fractions are needed for in vitro sensitization. Upon in vitro sensitization, a change in density occurs and all the “active” cells appear in the top two (A and B) fractions of the gradient. Of the five subpopulations of C57 bone marrow, obtained after density gradient centrifugation, the top 2 (A and B) fractions are required for in vitro sensitization. Upon in vitro sensitization, a change in density occurs again but now the active cells are distributed among the intermediate bands, B and C. The results indicate that subpopulations of lymph node cells and bone marrow cells interact during in vitro sensitization to transplantation antigens.