Analysis of cytokine production by helper T (Th) cells has revealed that functionally distinct subsets of CD4+ T cells exist that produce different cytokines and that eliminate different types of pathogens. The existence of these subsets illustrates how the immune system mounts specialized responses that are optimized to combat diverse microbes. For example, intracellular microbes such as mycobacteria are ingested by phagocytes but resist intracellular killing. The adaptive immune response to such microbes results in the activation of the phagocytes, enabling them to kill the ingested microbes. In contrast, the immune response to helminths is dominated by the production of immunoglobulin E (IgE) antibodies and the activation of eosinophils, which destroy the helminths. The immune response to extracellular bacteria and fungi requires cytokines that help to drive neutrophilic inflammation, because neutrophils in large numbers are needed to eliminate these pathogens. All these types of immune responses depend on CD4+ helper T cells, but for many years it was not clear how the CD4+ helper cells are able to stimulate such distinct immune effector mechanisms. We now know that these responses are mediated by subpopulations of CD4+ effector T cells that produce different cytokines.

CD4+ helper T cells may differentiate into three subsets of effector cells that produce distinct sets of cytokines that function to defend against different types of microbial infections in tissues, and a fourth subset that activates B cells in secondary lymphoid organs (Fig. 1). The subsets that were defined first are called Th1 cells and Th2 cells (for type 1 helper T cells and type 2 helper T cells, respectively); the third population, which was identified later, is called Th17 cells because its signature cytokine is interleukin (IL) 17. The T cells that help B lymphocytes, called follicular helper T (Tfh) cells. The discovery of these subpopulations has been an important mile stone in understanding immune responses and provides models for studying the process of cell differentiation. However, it should be noted that some activated CD4+ T cells may produce mixtures of cytokines and therefore cannot be readily classified into these subsets, and there may be plasticity in these populations so that one subset may convert into another under some conditions. Despite these caveats, considering the functions of CD4+ effector cells in the context of the major subsets is helpful for understanding the mechanisms of cell- mediated immunity.

Fig1. Characteristics of subsets of CD4+ helper T lymphocytes. A naive CD4+ T cell may differentiate into subsets that produce different cytokines that recruit and activate different cell types (referred to as target cells) and combat different types of infections in host defense. These subsets also are involved in various kinds of inflammatory diseases. The table summarizes the major differences among Th1, Th2, Th17, and Tfh subsets of helper T cells. IFN, Interferon; IL, interleukin.

The cytokines produced in adaptive immune responses include those made by the Th subsets, as well as cytokines produced by CD4+ regulatory T cells and CD8+ T cells. These cytokines of adaptive immunity share some general properties, but they each have different biologic activities and play unique roles in the effector phase or regulation of these responses (Fig. 2). The functions of the CD4+ T cell subsets reflect the actions of the cytokines they produce. Similar sets of cytokines may be produced early in immune responses by innate lymphoid cells, such as ILC1, ILC2, and ILC3 , and later by Th1, Th2, and Th17 cells, respectively. These combined innate and adaptive responses with similar cytokine profiles and functional outcomes are sometimes grouped under “type 1 immunity,” “type 2 immunity,” and “type 3 immunity.”

Fig2. Properties of the major cytokines produced by CD4+ helper T lymphocytes

Each subset of CD4+ T cells develops in response to the types of microbes that subset is best at eradicating. Different microbes elicit the production of different cytokines from dendritic cells and other cells, and these cytokines drive the differentiation of antigen-activated T cells to one or another subset. We next discuss the functions and development of each of the major subsets of CD4+ effector T cells. 

مواضيع ذات صلة

Presentation of Antigens by B Lymphocytes to Helper T Cells

Functional Consequences of B Cell Activation by Antigen

Role of Innate Immune Signals in B Cell Activation

Antigen-Induced Signaling in B Cells

Phases and Types of Humoral Immune Responses

Resistance of Pathogenic Microbes to Cell -Mediated Immunity

Differentiation and Functions of CD8+ Cytotoxic T Lymphocytes

Th17 Cells

Th2 Cells

Th1 Cells

Decline of the Immune Response

Migration of T Lymphocytes in Cell- Mediated Immune Reactions