The T helper 1/T helper 2 paradigm

T-cell elaboration of cytokines contributes to both the regulation of immunoglobulin synthesis and secretion, and cell-mediated immunity. Subsets of CD4+ T lymphocytes are characterized on the basis of patterns of cytokine release: Th1 cells differ from Th2 cells in that Th1 cells produce IL-2 and IFN-g, whereas Th2 cells produce IL-4, IL-5, IL-9, IL-10, and IL-13, among other cytokines. Th2 cells promote preferential production of some immunoglobulin isotypes, whereas Th1 cells mediate delayed hypersensitivity responses and inhibit the proliferation of the Th2 cells. Unlike B cells, T cells must migrate to the sites within the body where antigen is found, because T-cell responses to pathogens are dependent on the T cell being in direct contact with the pathogenic antigen.

In adults, there are approximately 25 million to 100 million distinct “naïve” T cell clones that have never encountered antigen. In contrast, there are only several thousand T cells bearing receptors that recognize individual antigen. Naïve T cells are first given the task of determining whether or not antigen is present, and second, whether or not this antigen is a threat to the body. Dendritic cells are instrumental in presenting antigen to T cells and are found in secondary lymphoid organs. These organs collect and trap antigen that is present in other parts of the body. Naïve T cells begin to migrate to these lymphoid organs in a process known as “homing.” When a T cell encounters an antigen, a cascade is initiated that results in an approximate thousand-fold clonal expansion of T cells with identical antigen specificity. In time, the activated T cells acquire effector function and once again home a second time to areas of inflammation. At these sites of inflammation, the T cells interact with eosinophils, basophils, mast cells, and antigen-presenting cells. There is another set of effector cells that contact activated B cells in lymphoid tissue and facilitate humoral immune responses. Although most effector T cells die after the antigen is cleared, a few remain and become memory cells and are able to mount rapid immune responses when specific antigen returns.

In humans, Th1 cells produce IL-2, IFN-g, lymphotoxin, and possibly small amounts of IL-6, IL-10, and IL-13. Th2 cells produce IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13. Both Th1 and Th2 cells produce TNF-a, granulocyte macrophage colony-stimulating factor (GM-CSF), and chemokines. In reality, there is significant overlap in the types of cytokines produced by these cell populations. A third subset of T helper cells exists and is termed Th0. Th0 cells express cytokines inherent to both Th1 and Th2 cells.