Journal Article

Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection

Fuller, Michael J, Weinmann, Amy S, Lund, Frances E, Bachus, Holly, Bradley, John E, Ballesteros-Tato, André, Zajac, Allan J, Botta, Davide, Marquez-Lago, Tatiana T, Randall, Troy D, León, Beatriz

2017

Overview

Humoral immunity is necessary for controlling viral infection. Ballesteros-Tato and colleagues show that development of follicular regulatory T cells is prevented by high concentrations of interleukin 2 at the peak of viral infection, but resumes at later time points to suppress autoantibody production. Interleukin 2 (IL-2) promotes Foxp3 + regulatory T (T reg ) cell responses, but inhibits T follicular helper (T FH ) cell development. However, it is not clear how IL-2 affects T follicular regulatory (T FR ) cells, a cell type with properties of both T reg and T FH cells. Using an influenza infection model, we found that high IL-2 concentrations at the peak of the infection prevented T FR cell development by a Blimp-1-dependent mechanism. However, once the immune response resolved, some T reg cells downregulated CD25, upregulated Bcl-6 and differentiated into T FR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones. Thus, unlike its effects on conventional T reg cells, IL-2 inhibits T FR cell responses.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 13 / 13/31 / 13/51 / 631/250/127/1213 / 631/250/2152/1566/2493 / Analysis / Animals / Bcl protein / Bcl-6 protein / Biomedicine / Care and treatment / CD25 antigen / Cell Movement - genetics / Cell Movement - immunology / Cytokines / Diagnosis / Follicles / Forkhead Transcription Factors - genetics / Forkhead Transcription Factors - immunology / Forkhead Transcription Factors - metabolism / Foxp3 protein / Gene Expression Profiling - methods / Host-Pathogen Interactions - drug effects / Host-Pathogen Interactions - immunology / Immune response / Immunology / Infections / Infectious Diseases / Influenza / Interleukin 2 / Interleukin-2 - administration & dosage / Interleukin-2 - metabolism / Interleukin-2 - pharmacology / Interleukin-2 Receptor alpha Subunit - genetics / Interleukin-2 Receptor alpha Subunit - metabolism / Interleukins / Lymphocytes B / Lymphocytes T / Mice, Inbred C57BL / Mice, Knockout / Mice, Transgenic / Orthomyxoviridae - immunology / Orthomyxoviridae - physiology / Orthomyxoviridae Infections - immunology / Orthomyxoviridae Infections - metabolism / Orthomyxoviridae Infections - virology / Positive Regulatory Domain I-Binding Factor 1 / Proto-Oncogene Proteins c-bcl-6 - genetics / Proto-Oncogene Proteins c-bcl-6 - metabolism / T cell receptors / T-Lymphocytes, Helper-Inducer - drug effects / T-Lymphocytes, Helper-Inducer - immunology / T-Lymphocytes, Helper-Inducer - metabolism / T-Lymphocytes, Regulatory - drug effects / T-Lymphocytes, Regulatory - immunology / T-Lymphocytes, Regulatory - metabolism / Transcription Factors - genetics / Transcription Factors - immunology / Transcription Factors - metabolism