Defect in B cell function in HTLV III/LAV positive hemophilia patients

The capacity of the peripheral blood lymphocytes (PBL) to generate an antibody response in vitro T cell-dependent antigen ovalbumin was studied in 12 severe hemophilia patients who were otherwise in good health. PBL from four of 12 patients were not capable of generating such a response after stimulation in vitro, whereas all controls were normal. This negative plaque-forming cell (PFC) response coincided with the presence of antibodies directed toward human T-lymphotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV). Only one patient with antibodies against HTLV-III/LAV had a normal PFC response. The negative PFC response was not due to a deficient T helper cell activity, nor to an excessive T suppressor cell function. However, in the peripheral blood of these four patients, the presence of activated B cells that are refractory to antigen-specific T helper cell signals and secrete specific antibodies spontaneously could be demonstrated. Most of the patients showed a hyperimmunoglobulinemia. No correlation between the T4/T8 ratio and the level of the PFC response was demonstrable. From the data obtained in these investigations we raise the hypothesis that infection with HTLV-III/LAV in hemophilia patients will lead to in vivo (pre)activation of B cells that results in unresponsiveness or decreased response to antigen-specific signals.

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Defect in B cell function in HTLV III/LAV positive hemophilia patients

Blood ◽

10.1182/blood.v69.5.1388.1388 ◽

1987 ◽

Vol 69 (5) ◽

pp. 1388-1393 ◽

Cited By ~ 9

Author(s):

EJ Sjamsoedin-Visser ◽

CJ Heijnen ◽

BJ Zegers ◽

JW Stoop

Keyword(s):

B Cells ◽

Peripheral Blood ◽

Cell Function ◽

Cell Activity ◽

Peripheral Blood Lymphocytes ◽

T Helper Cell ◽

Helper Cell ◽

T Helper

Abstract The capacity of the peripheral blood lymphocytes (PBL) to generate an antibody response in vitro T cell-dependent antigen ovalbumin was studied in 12 severe hemophilia patients who were otherwise in good health. PBL from four of 12 patients were not capable of generating such a response after stimulation in vitro, whereas all controls were normal. This negative plaque-forming cell (PFC) response coincided with the presence of antibodies directed toward human T-lymphotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV). Only one patient with antibodies against HTLV-III/LAV had a normal PFC response. The negative PFC response was not due to a deficient T helper cell activity, nor to an excessive T suppressor cell function. However, in the peripheral blood of these four patients, the presence of activated B cells that are refractory to antigen-specific T helper cell signals and secrete specific antibodies spontaneously could be demonstrated. Most of the patients showed a hyperimmunoglobulinemia. No correlation between the T4/T8 ratio and the level of the PFC response was demonstrable. From the data obtained in these investigations we raise the hypothesis that infection with HTLV-III/LAV in hemophilia patients will lead to in vivo (pre)activation of B cells that results in unresponsiveness or decreased response to antigen-specific signals.

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T helper cell polarisation as a measure of the maturation of the immune response

Mediators of Inflammation ◽

10.1080/0929350310001619744 ◽

2003 ◽

Vol 12 (5) ◽

pp. 285-292 ◽

Cited By ~ 4

Author(s):

Scott B. Cameron ◽

Ellen H. Stolte ◽

Anthony W. Chow ◽

Huub F. J. Savelkoul

Keyword(s):

Immune Response ◽

T Cells ◽

Intracellular Cytokine Staining ◽

T Helper Cell ◽

Helper Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Intracellular Cytokine ◽

T Helper

Background:T helper cell polarisation is important under chronic immune stimulatory conditions and drives the type of the evolving immune response. Mice treated with superantigensin vivodisplay strong effects on Thsubset differentiation. The aim of the study was to detect the intrinsic capacity of T cells to polarise under variousex vivoconditions.Methods:Purified CD4+T cells obtained from superantigen-treated mice were cultured under Thpolarising conditionsin vitro. By combining intracellular cytokine staining and subsequent flow cytometric analysis with quantitative cytokine measurements in culture supernatants by enzyme-linked immunosorbent assay (ELISA), the differential Thpolarising capacity of the treatment can be detected in a qualitative and quantitative manner.Results and conclusions:BALB/c mice were shown to be biased to develop strong Th2 polarised immune responses using Th0 stimulation of purified CD4+T cells from phosphate-buffered saline-treated mice. Nevertheless, our analysis methodology convincingly showed that even in these mice, Toxic Shock Syndrome Toxin-1 treatmentin vivoresulted in a significantly stronger Th1 polarising effect than control treatment. Our results indicate that populations of Thcells can be assessed individually for their differential Th1 or Th2 maturation capacityin vivoby analysing robustin vitropolarisation cultures combined with intracellular cytokine staining and ELISA.

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CD4+ CD25+ Regulatory T Cells Control T Helper Cell Type 1 Responses to Foreign Antigens Induced by Mature Dendritic Cells In Vivo

Journal of Experimental Medicine ◽

10.1084/jem.20030654 ◽

2003 ◽

Vol 198 (2) ◽

pp. 259-266 ◽

Cited By ~ 169

Author(s):

Guillaume Oldenhove ◽

Magali de Heusch ◽

Georgette Urbain-Vansanten ◽

Jacques Urbain ◽

Charlie Maliszewski ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Peripheral Tolerance ◽

T Helper Cell ◽

Helper Cell ◽

T Helper

Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II–restricted interferon γ–producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.

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ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling

Blood ◽

10.1182/blood-2009-10-250415 ◽

2010 ◽

Vol 116 (17) ◽

pp. 3208-3218 ◽

Cited By ~ 11

Author(s):

Daniel B. Graham ◽

Holly M. Akilesh ◽

Grzegorz B. Gmyrek ◽

Laura Piccio ◽

Susan Gilfillan ◽

...

Keyword(s):

Dendritic Cells ◽

Mhc Class Ii ◽

Autoimmune Encephalitis ◽

Class Ii ◽

T Helper Cell ◽

Helper Cell ◽

Nucleotide Exchange ◽

T Helper

Abstract Immature dendritic cells (DCs) specialize in antigen capture and maintain a highly dynamic pool of intracellular major histocompatibility complex class II (MHCII) that continuously recycles from peptide loading compartments to the plasma membrane and back again. This process facilitates sampling of environmental antigens for presentation to T helper cells. Here, we show that a signaling pathway mediated by the DC immunoreceptor tyrosine-based activation motif (ITAM)–containing adaptors (DAP12 and FcRγ) and Vav family guanine nucleotide exchange factors controls the half-life of surface peptide-MHCII (pMHCII) complexes and is critical for CD4 T-cell triggering in vitro. Strikingly, mice with disrupted DC ITAMs show defective T helper cell priming in vivo and are protected from experimental autoimmune encephalitis. Mechanistically, we show that deficiency in ITAM signaling results in increased pMHCII internalization, impaired recycling, and an accumulation of ubiquitinated MHCII species that are prematurely degraded in lysosomes. We propose a novel mechanism for control of T helper cell priming.

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In vivo administration of Fab′ fragments of anti-L3T4 (GK1.5) antibody inhibits the T helper cell function of murine lymph node cells

Cellular Immunology ◽

10.1016/0008-8749(89)90175-5 ◽

1989 ◽

Vol 120 (1) ◽

pp. 75-81

Author(s):

Nancy E. Street ◽

Koichi Uyemura ◽

Virginia M. Sanders ◽

Jonathan W. Uhr ◽

Ellen S. Vitetta

Keyword(s):

Lymph Node ◽

Cell Function ◽

T Helper Cell ◽

Helper Cell ◽

T Helper ◽

Fab Fragments ◽

Lymph Node Cells ◽

In Vivo Administration

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Two Ly-2 T helper cell subsets distinguished by Qa-1 phenotype. The priming environment determines whether one or both subsets will be generated.

Journal of Experimental Medicine ◽

10.1084/jem.155.3.831 ◽

1982 ◽

Vol 155 (3) ◽

pp. 831-838 ◽

Cited By ~ 6

Author(s):

J S McDougal ◽

F W Shen ◽

S P Cort ◽

J Bard

Keyword(s):

T Cells ◽

B Cells ◽

Cell Activity ◽

T Helper Cell ◽

T Cell Subsets ◽

Helper Cell ◽

T Helper ◽

Effector Cells ◽

Helper Activity ◽

Effector Activity

The Qa-1 cell surface phenotype reportedly distinguishes two Ly-1 T cell subsets conjointly required for T helper effector activity. Ly-1 cells, obtained from several different priming regimens, were negatively selected with anti-Qa-1 plus complement and compared with unselected Ly-1 cells for helper cell activity. Priming isolated T cells on antigen-pulsed macrophages in the absence of B cells favors the generation of the Ly-1:Qa1- subset, which is capable of efficient helper activity in the absence of the Ly-1:Qa-1+ subset. Priming T cells in an environment containing B cells generates both Ly-1:Qa-1- helper effector cells and Ly-1:Qa-1+ cells which contribute to the helper effect. Whether Ly-1:Qa-1+ cells are capable of independent helper activity cannot be determined, and, as such, Ly-1:Qa-1+ cells are more appropriately termed "help associated" rather than "helper effector." Our results assign a membrane phenotype, Qa-1, which distinguishes an Ly-1 help-associated B cell requiring subset in our system and may prove to be a general marker in a number of systems of Ly-1 inducer cell subsets which functionally require or recognize B cells or their products.

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Effect of a Recombinant CD4-IgG on In Vitro T Helper Cell Function: Data from a Phase I/II Study of Patients with AIDS

The Journal of Infectious Diseases ◽

10.1093/infdis/168.4.1012 ◽

1993 ◽

Vol 168 (4) ◽

pp. 1012-1016 ◽

Cited By ~ 5

Author(s):

M. Clerici ◽

R. Yarchoan ◽

S. Blatt ◽

C. W. Hendrix ◽

A. J. Ammann ◽

...

Keyword(s):

Phase I ◽

Cell Function ◽

T Helper Cell ◽

Helper Cell ◽

T Helper ◽

Function Data

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Defective T suppressor-inducer cell function in human immune deficiency virus-seropositive hemophilia patients

Blood ◽

10.1182/blood.v72.5.1474.bloodjournal7251474 ◽

1988 ◽

Vol 72 (5) ◽

pp. 1474-1477

Author(s):

LJ Sjamsoedin-Visser ◽

CJ Heijnen ◽

BJ Zegers ◽

JW Stoop

Keyword(s):

Immune Deficiency ◽

B Cells ◽

Cell Function ◽

Suppressor Cell ◽

T Helper Cell ◽

Helper Cell ◽

Human Immune Deficiency Virus ◽

T Helper ◽

Human Immune ◽

Hiv Seropositive

In human immune deficiency virus (HIV)-seropositive hemophilia patients, a low number of CD4 + lymphocytes is found, as well as a low CD4+/CD8+ ratio. In previous studies, it has been shown that antigen- specific T-helper cell (CD4+) function was present and no excessive antigen-specific T-suppressor cell (CD8+) function could be demonstrated. In this report, we studied another activity of CD4+ cells, namely the capacity to induce T-suppressor cell activity. The results clearly show a selective dysfunction of CD4+ suppressor-inducer (Tsi) cell function. Since these HIV-seropositive hemophilia patients showed the presence of activated B cells in the peripheral circulation refractory to antigen-specific T-helper cell signals and secreting specific antibodies spontaneously, we raised the hypothesis that the activated B cells in the patients activate the Tsi cells in vivo. This constant activation leads to a functional exhaustion of the Tsi cell pool.

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