A syngeneic splenic cell antigen induces a suppressor T cell in lymph nodes that controls cytotoxic T-cell and primary antibody responses

In chronic silicosis, mechanisms leading to lymphocyte activation are still poorly understood, although it is well known that not only the lung but also the draining lymph nodes are affected. In the present study, we investigated T-cell activation by analysis of cytokine expression in the enlarged thoracic lymph nodes of rats 2 mo after an 8-day silica aerosol exposure. In the case of helper T cell (Th) type 1 cytokines, we found a significant increase in interferon (IFN)-γ mRNA expression, whereas interleukin (IL)-2 expression remained unchanged. In contrast, gene transcription for the Th2-type cytokines IL-4 and IL-10 was diminished. In addition, with use of an in vitro lymphocyte-macrophage coculture system, an enhanced IFN-γ and a reduced IL-10 release were shown with cells from silicotic animals. With regard to IFN-γ-inducing cytokines, we observed enhanced IL-12 mRNA levels in vivo, whereas IL-18 gene expression was slightly decreased. These data indicate that a persistent shift toward an IFN-γ-dominated type 1 (Th1/cytotoxic T cell type 1) T-cell reaction pattern occurred within the thoracic lymph nodes of silicotic animals. Thus a mutual activation of lymphocytes and macrophages may maintain the chronic inflammatory changes that characterize silicosis.

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In situ quantitation of lymph node helper, suppressor, and cytotoxic T cell subsets in AIDS

Blood ◽

10.1182/blood.v67.3.596.596 ◽

1986 ◽

Vol 67 (3) ◽

pp. 596-603 ◽

Cited By ~ 22

Author(s):

GS Wood ◽

BF Burns ◽

RF Dorfman ◽

RA Warnke

Keyword(s):

T Cell ◽

Lymph Nodes ◽

Germinal Center ◽

Feedback Inhibition ◽

Cell Subset ◽

Suppressor Cells ◽

T Cell Subsets ◽

Cytotoxic T Cell ◽

B Cell Differentiation ◽

T Cell Subset

Abstract We have used the novel monoclonal antibodies 9.3 and anti-Leu-8 in conjunction with other T cell markers to quantify T cell subpopulations in the paracortex, mantle, and germinal center compartments of frozen sections of lymph nodes from seven homosexual men with acquired immunodeficiency syndrome (AIDS) and five heterosexual controls. Antibody 9.3 allows dissection of the Leu-2+ cytotoxic/suppressor subset (Tcs) into 9.3+ cytotoxic cells (Tc) and 9.3- suppressor cells (Ts). Anti-Leu-8 allows dissection of the Leu-3+ helper subset (TH) into functionally distinct subpopulations. The data indicate that the T cells in patients with AIDS exhibit normal antigen expression but altered subset ratios. In this series, the data suggested that the reversal of the paracortical TH-Tcs ratio was due to an increase in Ts with a concomitant decrease in TH and Tc. These changes were also reflected in a reversal of the normal paracortical Tc-Ts ratio (3.0) to less than 1.0. Furthermore, the data suggested a marked decrease in paracortical Leu-3+8+TH, which are known to have inducer function in cellular immune reactions and exert feedback inhibition of immunoglobulin production through a suppressor T cell intermediary. In contrast, there was preservation of the Leu-3+8-TH population within the germinal center. This T cell subset is known to help B cell differentiation. This microenvironmentally specific constellation of T cell subset alterations within lymph nodes may in part explain several of the immunologic findings associated with AIDS.

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A peptide-free, liposome-based oligosaccharide vaccine, adjuvanted with a natural killer T cell antigen, generates robust antibody responses in vivo

Chemical Science ◽

10.1039/c3sc53471e ◽

2014 ◽

Vol 5 (4) ◽

pp. 1437-1441 ◽

Cited By ~ 18

Author(s):

S. Deng ◽

L. Bai ◽

R. Reboulet ◽

R. Matthew ◽

D. A. Engler ◽

...

Keyword(s):

T Cell ◽

Natural Killer ◽

Antibody Responses ◽

Natural Killer T Cell ◽

Cell Antigen ◽

Killer T Cell ◽

Natural Killer T

Vaccination of mice with liposomes containing an oligosaccharide and a natural killer T cell agonist results in generation of high titers of antibodies (IgM and IgG) for the oligosaccharide.

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Exploring the Mechanisms of Primary Antibody Responses to T Cell-Dependent Antigens

Journal of Theoretical Biology ◽

10.1006/jtbi.1996.0127 ◽

1996 ◽

Vol 181 (3) ◽

pp. 215-235 ◽

Cited By ~ 26

Author(s):

Mihaela Oprea ◽

Alan S. Perelson

Keyword(s):

T Cell ◽

Antibody Responses ◽

Primary Antibody

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In situ quantitation of lymph node helper, suppressor, and cytotoxic T cell subsets in AIDS

Blood ◽

10.1182/blood.v67.3.596.bloodjournal673596 ◽

1986 ◽

Vol 67 (3) ◽

pp. 596-603

Author(s):

GS Wood ◽

BF Burns ◽

RF Dorfman ◽

RA Warnke

Keyword(s):

T Cell ◽

Lymph Nodes ◽

Germinal Center ◽

Feedback Inhibition ◽

Cell Subset ◽

Suppressor Cells ◽

T Cell Subsets ◽

Cytotoxic T Cell ◽

B Cell Differentiation ◽

T Cell Subset

We have used the novel monoclonal antibodies 9.3 and anti-Leu-8 in conjunction with other T cell markers to quantify T cell subpopulations in the paracortex, mantle, and germinal center compartments of frozen sections of lymph nodes from seven homosexual men with acquired immunodeficiency syndrome (AIDS) and five heterosexual controls. Antibody 9.3 allows dissection of the Leu-2+ cytotoxic/suppressor subset (Tcs) into 9.3+ cytotoxic cells (Tc) and 9.3- suppressor cells (Ts). Anti-Leu-8 allows dissection of the Leu-3+ helper subset (TH) into functionally distinct subpopulations. The data indicate that the T cells in patients with AIDS exhibit normal antigen expression but altered subset ratios. In this series, the data suggested that the reversal of the paracortical TH-Tcs ratio was due to an increase in Ts with a concomitant decrease in TH and Tc. These changes were also reflected in a reversal of the normal paracortical Tc-Ts ratio (3.0) to less than 1.0. Furthermore, the data suggested a marked decrease in paracortical Leu-3+8+TH, which are known to have inducer function in cellular immune reactions and exert feedback inhibition of immunoglobulin production through a suppressor T cell intermediary. In contrast, there was preservation of the Leu-3+8-TH population within the germinal center. This T cell subset is known to help B cell differentiation. This microenvironmentally specific constellation of T cell subset alterations within lymph nodes may in part explain several of the immunologic findings associated with AIDS.

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Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization

Journal of Experimental Medicine ◽

10.1084/jem.188.6.1075 ◽

1998 ◽

Vol 188 (6) ◽

pp. 1075-1082 ◽

Cited By ~ 413

Author(s):

Angel Porgador ◽

Kari R. Irvine ◽

Akiko Iwasaki ◽

Brian H. Barber ◽

Nicholas P. Restifo ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Lymph Nodes ◽

Antigen Presentation ◽

Cd8 T Cells ◽

Cytotoxic T Cell ◽

Gene Gun ◽

Cross Presentation

Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes (LNs). Under these conditions, two possible modes of DC antigen presentation to naive CD8+ T cells might exist: (a) presentation directly by gene-transfected DC trafficking to local lymph nodes, and (b) cross-presentation by untransfected DC of antigen released from or associated with transfected epidermal cells. The relative contributions of these distinct modes of antigen presentation to priming for cytotoxic T cell (CTL) responses have not been clearly established. Here we show that LN cells directly expressing the DNA-encoded antigen are rare; 24 h after five abdominal skin bombardments, the number of these cells does not exceed 50–100 cells in an individual draining LN. However, over this same time period, the total number of CD11c+ DC increases more than twofold, by an average of 20,000–30,000 DC per major draining node. This augmentation is due to gold bombardment and is independent of the presence of plasmid DNA. Most antigen-bearing cells in the LNs draining the site of DNA delivery appear to be DC and can be depleted by antibodies to an intact surface protein encoded by cotransfected DNA. This finding of predominant antigen presentation by directly transfected cells is also consistent with data from studies on cotransfection with antigen and CD86-encoding DNA, showing that priming of anti-mutant influenza nucleoprotein CTLs with a single immunization is dependent upon coexpression of the DNAs encoding nucleoprotein and B7.2 in the same cells. These observations provide insight into the relative roles of direct gene expression and cross-presentation in CD8+ T cell priming using gene gun immunization, and indicate that augmentation of direct DC gene expression may enhance such priming.

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