CD4-expressing T cells are helper T cells that provide assistance to B cells and guide their differentiation into plasma cells. This function requires both the production and secretion of cytokines such as IL-4 as well as direct contact between the helper T cell and the B cell to which it provides help.

A second class of helper T cell has as its major function secreting the cytokines that contribute to the establishment of an inflammatory environment. Multiple subtypes of such inflammatory T cells are categorized based on the spectrum of different cytokines they produce and their respective roles in regulating immune responses. Whereas all activated T cells can produce IL-2, other cytokines are produced only by particular helper T-cell subsets. These helper T cells are classified as T_H1 cells, which secrete interferon γ and tumor necrosis factor (TNF), and T_H2 cells, which secrete IL-4 and IL-10. T_H1 cells, through production of interferon γ, can activate macrophages and stimulate an inflammatory response. Referred to also as inflammatory T cells, T_H1 cells nonetheless play an important role in antibody production, notably facilitating the production of complement-fixing antibodies such as IgG1 and IgG3. T_H2 cells, through production of IL-4, play an important role in B-cell responses that involve class switching to the IgG1 and IgE isotypes (discussed above). Recall that in B cells, the induction of activation-induced deaminase (AID) prepares the B cell for class-switch recombination and somatic hypermutation. This induction is a consequence of the precise mixture of cytokines produced by helper T cells and the binding of a surface membrane protein on the activated T cell, CD40, to a protein on the B-cell surface, CD40 ligand (CD40L).

Conventional helper T cells can also differentiate into T_H17 cells, which produce IL-17, and into induced regulatory T cells (induced Tregs, distinct from the natural Tregs generated in the thymus). Both types of Treg cells attenuate immune responses by exerting a suppressive effect on other types of T cells. Natural Tregs restrain the activity of potentially self-reactive T cells and are important in maintaining peripheral tolerance (the absence of an immune response to self antigens), whereas induced Tregs are believed to regulate excessively strong immune responses against foreign antigens. T_H17 cells are important in defense against bacteria (extracellular bacteria in particular) and also play a pathogenic role in autoimmune diseases.