Accumulation of CD25+ CD4+ T-cells in the draining lymph node during the elicitation phase of DNCB-induced contact hypersensitivity in lambs

Contact hypersensitivity (CHS) is a T cell-mediated response to hapten sensitization of the epidermis. The roles of CD4+ and CD8+ T cells in CHS have remained unclear, however, as studies to define either subset as the T cells mediating CHS have provided conflicting results. The goal of this study was to correlate the in vivo function of CD4+ and CD8+ T cells in CHS with the cytokines produced by each T cell population. Antibody-mediated depletion of CD4+ T cells before sensitization of BALB/c mice with 2,4-dinitrofluorobenzene (DNFB) or oxazolone (Ox) resulted in increased and prolonged CHS responses, indicating CD4+ T cells as negative regulators of the response. Depletion of CD8+ T cells resulted in low or abrogated responses, indicating CD8+ T cells as the effector cells in CHS. Sensitization with DNFB or Ox induced lymph node cell populations of CD8+ T cells producing interferon (IFN)-gamma and no interleukin (Il) 4 or Il-10, and CD4+ T cells producing Il-4 and Il-10 and no or little detectable IFN-gamma. The polarized patterns of cytokine production were stimulated by culture of hapten-primed lymph node cells either on anti-T cell receptor antibody-coated wells or with semipurified Langerhans cells isolated from hapten-sensitized mice. Stimulation of cytokine production during culture of hapten-primed CD4+ or CD8+ T cells with Langerhans cells was hapten specific and restricted to class II or class I major histocompatibility complex, respectively. The induction of the CD4+ and CD8+ T cells producing the polarized patterns of cytokines was not restricted to BALB/c mice, as cells from Ox sensitized C57B1/6 and B10.D2 mice produced the same patterns. Collectively, these results expose the induction of two polarized and functionally opposing populations of T cells by hapten sensitization to induce CHS: IFN-gamma-producing effector CD8+ T cells and Il-4/Il-10-producing CD4+ T cells that negatively regulate the response.

Download Full-text

Novel Lymph Node Trafficking Patterns of CD4 T Cells During Tolerization.

Transplantation Journal ◽

10.1097/00007890-201407151-01281 ◽

2014 ◽

Vol 98 ◽

pp. 391

Author(s):

B. Burrell ◽

K. Warren ◽

J. Bromberg

Keyword(s):

T Cells ◽

Lymph Node ◽

Cd4 T Cells

Download Full-text

Antigen presentation to naive CD4 T cells in the lymph node

Nature Immunology ◽

10.1038/ni957 ◽

2003 ◽

Vol 4 (8) ◽

pp. 733-739 ◽

Cited By ~ 305

Author(s):

Andrea A Itano ◽

Marc K Jenkins

Keyword(s):

T Cells ◽

Lymph Node ◽

Antigen Presentation ◽

Cd4 T Cells

Download Full-text

Intravenous Arginine Administration Benefits CD4+ T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis

Nutrients ◽

10.3390/nu12041047 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1047

Author(s):

Chiu-Li Yeh ◽

Sharon Angela Tanuseputero ◽

Jin-Ming Wu ◽

Yi-Ru Tseng ◽

Po-Jen Yang ◽

...

Keyword(s):

T Cells ◽

Single Dose ◽

Lymph Node ◽

T Cell ◽

Lymph Nodes ◽

Cd4 T Cells ◽

Cd4 T Cell ◽

Liver Inflammation ◽

Aortic Lymph Node ◽

Inos Inhibitor

This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4+ T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4+ T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4+ T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4+ T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4+ T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis.

Download Full-text

The race for the prize: T-cell trafficking strategies for optimal surveillance

Blood ◽

10.1182/blood-2012-04-424655 ◽

2012 ◽

Vol 120 (7) ◽

pp. 1432-1438 ◽

Cited By ~ 23

Author(s):

Minyi Lee ◽

Judith N. Mandl ◽

Ronald N. Germain ◽

Andrew J. Yates

Keyword(s):

T Cells ◽

Lymph Node ◽

T Cell ◽

Optimization Problem ◽

Cell Trafficking ◽

T Cell Trafficking ◽

Cell Responses ◽

Major Histocompatibility Complexes ◽

Draining Lymph Node ◽

Slow Transit

Abstract The initiation of T-cell responses requires rare precursors to locate a draining lymph node (dLN) and encounter dendritic cells (DCs) presenting peptide-major histocompatibility complexes (pMHCs). To locate this needle in the haystack rapidly, T cells face an optimization problem—what is the most efficient trafficking strategy for surveillance and recirculation through blood? Two extremes are scanning low numbers of DCs per node with frequent recirculation, or meticulous surveillance with infrequent recirculation. Naive T cells also require stimulation by self-pMHCs. To enable efficient location of both foreign and self, has evolution settled on an optimum time for T cells to spend surveying each lymph node? Using a data-driven mathematical model, we show the most efficient strategy for detecting antigen in a dLN depends on its abundance. Detection of low-density antigen is optimized with systemically slow transit. In contrast, at high densities or if dLN egress is restricted, rapid transit through other nodes is optimal. We argue that blood-lymph recirculation dynamics facilitate a trade-off, and are consistent with dominant roles for the very early detection of rare foreign antigens in a dLN, and the efficient accumulation of signals from systemically distributed self-antigens.

Download Full-text