Helper T lymphocytes, or T-helper (Th) cells, can be assigned to one of several subsets, including the following:

• Helper T type 1 (Th1) cells are responsible for cell- mediated effector mechanisms.

 • Helper T type 2 (Th2) cells play a greater role in the regulation of antibody production.

• Regulatory T (Treg) cells are an immunoregulatory type of Th cells.

These divisions are not absolute, with considerable overlap or redundancy in function among the different subsets. This classification is based on the in vitro blends of cytokines that they produce. Th1 and Th2 cells can promote the development of cytotoxic cells and are believed to develop from Th0 cells. T h1 cells interact most effectively with mononuclear phagocytes; Th2 cells release cytokines that are required for B cell differentiation (Fig. 1).

Fig1. Differentiation of naïve CD4+ helper T (Th) cells into Th1 and Th2 effector cells. After their activation by antigen and  costimulators, naïve helper T cells may differentiate into Th1 and Th2  cells under the influence of cytokines. IL-12 produced by microbe activated macrophages and dendritic cells stimulates differentiation  of CD4+ T cells into Th1 effectors. In the absence of IL-12, the T cells  themselves (and perhaps other cells) produce IL-4, which stimulates  their differentiation into Th2 effectors. (Adapted from Abbas AK, Lichtman AH: Basic immunology: functions and disorders of the immune system, ed 3, Philadelphia, 2008, Saunders.)

Characterized by high interferon-gamma (IFN-γ) production, Th1 responses promote the elimination of intracellular pathogens (Fig. 2, A). Characterized by IL-4 and IL-5, Th2 responses promote a different type of effector response that involves immunoglobulin E (IgE) production and eosinophils capable of eliminating larger extracellular pathogens, such as helminths (see Fig. 2, B). In situations of repeated pathogen exposure or persistent infection, the polarization of T cell responses serves to focus the antigen-specific response on a specific effector pathway.

Fig2. Functions of Th1 and Th2 subsets of CD4+ helper T lymphocytes. A, Th1 cells produce the cytokine IFN-γ, which activates phagocytes to kill ingested microbes and stimulates the production of antibodies that promote the ingestion of microbes by the phagocytes. B, Th2 cells  specific for microbial or nonmicrobial protein antigens produce the cytokines IL-4, which stimulates the production of IgE antibody, and IL-5,  which activates eosinophils. IgE participates in the activation of mast cells by protein antigens and coats helminths for destruction by eosinophils.  Th2 cells also stimulate the production of other antibodies (IgG4 in humans) that neutralize microbes and toxins but do not bind to Fc receptors or  activate complement efficiently. (Adapted from Abbas AK, Lichtman AH: Basic immunology: functions and disorders of the immune system, ed 3, Philadelphia, 2008, Saunders.)

The following factors can influence the terminal differentiation of lymphocytes:

 • Type of antigen-presenting cell (APC)

• Affinity of the specific antigenic peptide

 • Types of costimulatory molecules expressed by APCs

• Cytokines acting on T cells during primary activation through TCRs

A hierarchy is apparent among these factors and is determined by how they influence T cell differentiation. Certain cytokines acting directly on T cells during primary activation appear to be the most proximal or direct mediators of CD4+ T cell differentiation. The presence of IL-12 during primary T cell activation leads to strong development of Th1 responses, and IL-4 promotes Th2 development. Activation through the TCR is a requirement for initiating terminal differentiation, but the signals from the TCR appear to be phenotype-neutral.

Certain T cells carry out delayed hypersensitivity reactions. These T cells react with antigen MHC class II on APCs and create their effects mainly through cytokine production. These cells generally are of the CD4+ phenotype.

T cells can also be differentiated into two populations depending on whether they use an αβ (TCR2) or γδ (TCR1) antigen receptor. The TCR consists of a heterodimer and a number of associated polypeptides that form the CD3 complex. The dimer recognizes processed antigen associated with an MHC molecule. The CD3 complex is required for receptor expression and is involved in signal transduction. TCR1 cells constitute less than 5% of total lymphocytes but appear in greater proportions in some sites (e.g., skin, vagina). TCR1 cells appear to recognize different antigens than TCR2 cells, including carbohydrate and intact protein antigens. In addition, some TCR1 cells do not require antigen to be processed or presented by MHC molecules.

مواضيع ذات صلة

T Regulatory Lymphocytes

Sites of Lymphocyte Development

MONOCYTE-MACROPHAGE DISORDERS

Clinical Features of HIV Infection and AIDS

Pathogenesis of AIDS

Congenital Immunodeficiencies : Defects in Lymphocyte Activation and Function

Congenital Immunodeficiencies: Defects in Lymphocyte Maturation

Congenital Immunodeficiencies: Defects in Innate Immunity

Congenital (Primary) Immunodeficiencies

Neuroimmunology: Interactions Between the Immune and Nervous Systems

Disorders of Neutrophils

Cell Surface Receptors