Polarization Of T Cell Cytokine Responses

Cytokines are secreted by immune cells and can either stimulate or suppress the activity of immune cells and alter each cell's pattern of cytokine expression.[5] They

Fig. 1 Cells regulating immune responses. Blood immune cells. Immune cells that circulate in blood are shown. All immune cells in the blood, the hematopoietic cells, are derived from bone marrow stem cells. These hematopoietic stem cells give rise to two main lineages: one for lymphoid cells (lymphoid progenitor) and one for myeloid cells (myeloid progenitor). The common lymphoid progenitor will differentiate into either T cells or B cells depending on the tissue to which it travels (homes). In mammals, T cells develop in the thymus while B cells develop in the fetal liver and bone marrow. Pigs use special areas of their intestines, termed the Peyer's patches, for B cell maturation. B cells produce the antibodies so crucial to immune and vaccine responses. To produce antibodies, B cells must become antibody forming cells (AFC), or plasma cells. Innate immune responses are carried out by natural killer (NK) cells that also derive from the common lymphoid progenitor cell. The myeloid cells differentiate into the committed cells on the left. The platelets help blood to clot and thus heal injured tissue. Three other myeloid derived cell types, the monocyte, macrophage and dendritic cells are critical in helping the immune system recognize what is foreign, and thus stimulating specific immune system responses. Finally, the ''granulocytes'', a term used for eosinophils, neutrophils and basophils, have specialized functions, e.g., neutrophils will use antibodies to trap and kill invading bacteria. (Picture used with permission of National Hog Farmer.) Adapted from http://www.ed.sc.edu:85/book/immunol sta.htm. Courtesy of Department of Pathology & Microbiology, University of South Carolina School of Medicine, Columbia, SC. (View this art in color at www.dekker.com.)

Fig. 1 Cells regulating immune responses. Blood immune cells. Immune cells that circulate in blood are shown. All immune cells in the blood, the hematopoietic cells, are derived from bone marrow stem cells. These hematopoietic stem cells give rise to two main lineages: one for lymphoid cells (lymphoid progenitor) and one for myeloid cells (myeloid progenitor). The common lymphoid progenitor will differentiate into either T cells or B cells depending on the tissue to which it travels (homes). In mammals, T cells develop in the thymus while B cells develop in the fetal liver and bone marrow. Pigs use special areas of their intestines, termed the Peyer's patches, for B cell maturation. B cells produce the antibodies so crucial to immune and vaccine responses. To produce antibodies, B cells must become antibody forming cells (AFC), or plasma cells. Innate immune responses are carried out by natural killer (NK) cells that also derive from the common lymphoid progenitor cell. The myeloid cells differentiate into the committed cells on the left. The platelets help blood to clot and thus heal injured tissue. Three other myeloid derived cell types, the monocyte, macrophage and dendritic cells are critical in helping the immune system recognize what is foreign, and thus stimulating specific immune system responses. Finally, the ''granulocytes'', a term used for eosinophils, neutrophils and basophils, have specialized functions, e.g., neutrophils will use antibodies to trap and kill invading bacteria. (Picture used with permission of National Hog Farmer.) Adapted from http://www.ed.sc.edu:85/book/immunol sta.htm. Courtesy of Department of Pathology & Microbiology, University of South Carolina School of Medicine, Columbia, SC. (View this art in color at www.dekker.com.)

regulate a broad range of actions resulting in antigen-specific immune responses, alterations in levels of other cytokines, chemokine secretion, Ig production and isotype maturation, eosinophil and mast cell recruitment and activation, and cytotoxic T cell generation.1-3-1 To counteract these mediators of host defense, certain infectious organisms actually encode their own cytokine modulators or receptor-blocking proteins.

Once activated, CD4+ T cells produce specific sets of cytokine signals. CD4+ T helper 1 (Th1) cells express the cytokine IFN-g, which is essential for effective antiviral and bacterial responses (Table 2). In many species Th1 responses are amplified by the release of IL-12. Th1 cytokines activate macrophages and natural killer cells in response to internally processed antigens. CD4+ Th2 cells stimulate a different set of cytokines, including IL-4, IL-5, and IL-13 in response to external peptides. These Th2 cytokines increase mast cell and eosinophil numbers and activities and stimulate B cells to switch to IgA and IgE production, thus enhancing inflammatory and allergic responses.

Cytotoxic CD8+ T cells interact with infected cells or tumor cells via antigen presented by class I MHC. Cell conjugates stimulate TCR-encoded recognition processes.

Table 2 T cell subsets and their adaptive immune responses

T helper (Th) cells

Regulatory T cells (Treg)

T cell typea

Th1 CD4

Th2 CD4

Treg

Cytotoxic T cells (CTL)

Major CD marker

CD4 +

CD4 +

CD4+CD25+

CD8 +

CD4 +

Cell location of

Intracellular

Extracellular

Intracellularly

Extracellularly

microbe/

microbe

microbe

processed

processed

processed antigen

antigen

antigen

Dominant cytokines/

IFN g, IL 12

IL 4, IL 13

IL 10, TGFß

Perforins,

Perforins,

proteins

granzymes

granzymes

MHC/SLA

Class II

Class II

Class II

Class I

Class II

Size antigenic

6 8 amino

6 8 amino

9 12 amino

6 8 amino

peptide

acids

acids

acids

acids

aCD8+ cytokine secreting cells are noted as type I and type II cells, as they express IFN g, IL 12 or IL 4, IL 13, respectively.

aCD8+ cytokine secreting cells are noted as type I and type II cells, as they express IFN g, IL 12 or IL 4, IL 13, respectively.

CD8 + T cells can stimulate cytokine production similar to that by CD4+ T cells; they can also lyse infected cells. Lysis occurs by cytolytic processes, by signaling through death receptors and apoptotic pathways, or by stimulating release of enzymes (granzymes, perforins) from specialized organelles, thus resulting in degradation of the infected target cell.[2,3] Tumors and some viruses suppress immunity by causing infected cells to downregulate MHC expression or by secreting cytokines that modulate effector responses.

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