IL-2 Producing Memory CD4+ T Lymphocytes Are Closely Associated with the Generation of IgG-Secreting Plasma Cells

Abstract

The role of specific CD4+ T cell subsets in the induction of humoral immune responses in humans is largely unknown. In this study, the generation of hepatitis B surface Ag-specific CD4+ T lymphocytes following vaccination was closely monitored and characterized at the single-cell level. The appearance and absolute numbers of hepatitis B surface Ag-specific IL-2 producing effector memory CD4+ T lymphocytes was solely and tightly related to Ab titers reached. This relation remained present many years after vaccination. Subsequently, a relation was found between Ab titers and number of IL-2 producing memory CD4+ T lymphocytes for various other Ags. These observations matched the findings of an in vitro assay, using different T cell subsets to induce B cell differentiation into IgG-producing plasma cells. By depleting for IL-2 producing memory T cells, we demonstrated that these cells are important for B cell differentiation into IgG-producing plasma cells. Finally, blocking the action of IL-2 with an IL-2R-α Ab inhibited the differentiation of B lymphocytes into IgG-producing plasma cells. Based on these findings, we conclude that the development of Ag-specific IL-2-producing memory T cells appears to be essential for the development of IgG-secreting plasma cells in humans.

CD4 + T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

“…This is similar to reports that suggest that a relationship exists between the activation of IL-4-producing T-cell subsets and antibody production in a human system in which the immune response is induced by natural infection (44). Similarly, the number of IL-2-producing CD4 ϩ T cells was significantly higher against most of these PvTRAgs, a finding which is supported by a report that IL-2 produced by antigen-specific CD4 ϩ T cells promotes the growth and differentiation of antigen-specific B cells (45). These findings indicate a link between the activation of CD4 ϩ T cells and the generation of antibodies against PvTRAgs.…”

Tick-Borne Encephalitis (TBE) and Hepatitis B Nonresponders Feature Different Immunologic Mechanisms in Response to TBE and Influenza Vaccination with Involvement of Regulatory T and B Cells and IL-10

“…Yet, in vivo these donors are capable of generating TBE and influenza-specific Abs in a secondary/memory immune response. According to recent studies, secondary Ab responses require IL-2 production from proliferating, Ag-specific CD4 T cells, leading to induction of IgGproducing plasma cells and cognate T cell help (CD40/CD40L interaction) for Ig class switching (28,29). These observations raise the question of how hepatitis B nonresponders are capable of producing Ag-specific Ab titers, if abrogated T cell proliferation is not only an in vitro phenomenon but also present in vivo.…”

IL-21 signalling via STAT3 primes human naïve B cells to respond to IL-2 to enhance their differentiation into plasmablasts

“…Our data may also provide a mechanism for the positive correlation between the frequency of IL-2-producing Ag-specific memory CD4 1 T cells and IgG titers in vivo. 46 It is plausible that the IL-2 1 memory CD4 1 T cells examined 46 contained IL-21-producing Tfh cells. IL-2, IL-21, and their receptors share several structural and functional similarities.…”