T Cells in the Lymph Node

Cytokine/chemokine milieu induced by external, self and self-modified proteins, loaded into DCs/macrophages and delivered from affected tissues (including the brain) by lymph into regional draining lymph nodes controls the balance between induction of immunity or tolerance. Both the induction of antigen-specific immunity and tolerance rely on the direct interaction of DCs with naive T cells. These interactions occur in the T cell zone of lymph nodes in the vicinity of high endothelial venules (Von Andrian and Mackay, 2000). 

These follicular T cells strongly express the CD28-related molecule ICOS (inducible T-cell co-stimulator also known as CD278) and secrete moderate amounts of IL-10, CD278, and IL-10 act as co-sdmulatory factors having crucial functions in T helper cell and B-cell responses. After stimulation follicular 

CD4 Treg cells suppress Thl/Th2 cells function, the expansion of CD8+ cells and B-cell production of antibody. These are CD4 CD25 CD57 T cells that co-express CXCR5 and localize to T cell zone and germinal centers. T cells that express NKl.l (CD4 NKT cells) as well as NK are there. 

Spontaneous ectopic germinal-center formation has long been recognized to occur in human autoimmune diseases and is a source of somatically mutated high-affinity autoandbodies. 

Some polarized andgen-specific CD4 T cells (Thl, Th2), and-gen-primed CD8+ upregulate the expression of receptors for pro-inflammatory chemokines such as CXCR3 (CXCL9, -10, -11, known as a-chemokines IP-10, Mig, I-TAC) and down- 

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Indirect pathway. Recipient APCs migrate into the graft and phagocytize alloantigens. The donor MHC molecules then are expressed on the cell surfaces of the recipient s APCs and presented to recipient T cells in the lymph nodes. 

Suzuki, M., Ohwada, M., Saga, Y., Kohno, T., Takei, Y., and Sato, I. 2001. Micrometastatic p53-pos-itive cells in the lymph nodes of early stage epithelial ovarian cancer Prognostic significance. Oncology 60 170-175. 

A natural mutation in mice, the pit mutation, has helped to elucidate the role of CCR7 and its ligands. Mice homozygous for the mutation show impaired homing of T-cells to the lymph nodes and spleen (241). These mice also show a decreased number of interdigitating dendritic cells in lymph nodes. Recently, the pit mutation has been associated with a deletion that results in the lack of MIP-3 and reduced expression of SLC (242). The phenotype of pit mice reflects the role of CCR7 in dendritic and T-cell recruitment. 

HIV is relatively effective, but it is unable to completely clear the infection, and the patient enters a latent, asymptomatic or mildly symptomatic stage lasting 5 to 15 years. During this time, a high rate of viral replication can be seen in the lymph nodes. Eventually immune deficiency occurs when the body is no longer able to replenish helper T cells at a rate equal to that at which HIV is destroying them. 

Doganci A , Karwot R , Maxeiner JH 24 ( contributed equally), et al 1L-2R beta Chain Signaling Controls Immunosuppressive CD4 T Cells in the Draining Lymph Nodes and Lung during Allergic Airway Inflammation 25... 

Figure 17.41 The dose proximify of adipocytes to proliferating and developing cells in the bone marrow and the presence of a lymph node in an adipose tissue depot Note adipocytes in both Locations provide essential nutrients, i.e. fatty acids and glutamine. Proliferation of both B and T lymphocytes takes place in the lymph nodes (see below).

Skin is rich in dendritic cells, which are potent initiators of immune responses and possess the co-stimulatoiy and adhesion molecules required for T cell activation. In addition, dendritic cells possess a unique ability to process and present extracellular antigens in the context of both class I and class II molecules. Thus, transfection of plasmids into these cells is likely to elicit both cellular and humoral responses. Specific targeting of dendritic cells residing in the lymph nodes will likely represent an attractive strategy for providing a robust immune response with nucleic acid vaccines. 

Repeated JP-S Mouse IDO. 250,500,1,000, 2,500 mg/m, 1 hr/d for7d, inhalation (aerosolized) Dose-related decrease in spleen and thymus organ weights and decrease in total viable cells from those organs. At 100 and 250 mg/m1, loss of total cell numbers in the lymph nodes and peripheral blood, but an increase in bone marrow lota) cell numbers at 500 and 1,000 ing/m , increase in total cell numbers in lymph nodes and peripheral blood cell numbers, but a decrease in bone marrow cell numbers. Dose-related decrease in immune function observed in animals exposed to JP-8 and then treated with Concovalin-A D.T. Harris el al. 1997... 

Sedgwick, J.D. and Holt, P.G. (1985). Induction of IgE-secreting cells and IgE isotype-specific suppressor T cells in the respiratory lymph nodes of rats in response to antigen inhalation. Cell. Immunol. 94, 182-194. 

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