Fine-tuning of T cell responses during infection

doi:10.1016/j.coi.2009.07.004

Current Opinion in Immunology

Volume 21, Issue 4, August 2009, Pages 367-377

https://doi.org/10.1016/j.coi.2009.07.004 Get rights and content

“Everything in excess is opposed to nature”
Hippocrates

Adequate control of infection relies on development of a tailored immune response according to the requirements of a given infection. This is achieved by the continuous crosstalk between innate and adaptive immunity. Pathogen diversity is deciphered via a plethora of receptors converging signals to adaptor molecules; tissue sites and environment generate additional signals that further influence T cell lineage decisions. Within this continuum of interactions, fine-tuning of the ensuing T cell responses together with plasticity of the committed T cells ensure development of balanced immune responses maintaining homeostasis. This review focuses on the multiple mechanisms that govern T cell differentiation during infection.

Introduction

From the beginning of time, humans have lived and evolved in a world of microbes. Although only a minor proportion of microbial organisms have come into close contact with mammalian hosts, pressure imposed on host and pathogen has shaped their respective developments through coevolution. In this context, crucial factors for survival of the host include prompt recognition of invading pathogens, acquisition of an immune response that is constantly controlled and fine-tuned, pathogen eradication followed by as little collateral damage as possible and prompt return to homeostasis. Cell autonomous defense mechanisms exist in all metazoans, but only vertebrates evolved the highly sophisticated network of specialized cells of hematopoetic origin, which make up the immune system. Immunity evolved into a highly diverse and complex system composed of different layers of organization connected by highly elaborate regulatory networks. Yet, this complexity can be reduced to two major streams: the innate immune response that is less diversified but independent in action, and the adaptive immune response with enormous diversity but strong dependency on innate immunity and hence limited autonomy. This article focuses on recent insights into the intricate mechanisms by which innate immunity initiates and fine-tunes ensuing T cell responses during infection.

Section snippets

Infection, inflammation and T cell immunity

Invading microorganisms are recognized by specific sensors, the pattern recognition receptors (PRRs) [1^••], which trigger an inflammatory response upon ligand detection [2^••]. Subsequently, proinflammatory cytokines including TNF-α, IL-6, IL-1β, antimicrobial peptides, and mediators that modify endothelial properties are released. Naïve lymphocytes are recruited to sites of inflammation where they not only contact antigen-presenting cells (APC) but also face a milieu rich in soluble

The origin determines the outcome (Figure 1)

PRR comprise numerous receptors of different biochemical structure and intracellular location – Toll-like receptors (TLR), NOD-like receptors (NLR), C-type lectin receptors (CLR), RIG-like receptors (RLR), scavenger receptors (SR) – as well as different soluble receptors. Yet, the number of PRR is finite. To achieve the most appropriate response for dealing with different types of microbes, PRR form different combinations. Thus, the innate immune system seems able to dissect the pathogen into

Outlook

Although the past years have witnessed an enormous increment in knowledge of Th differentiation and the underlying signaling pathways that govern transition from Th0 to Th1, Th2, Th17, or Treg, less is known about the stability and plasticity of these developments. For a long time, stable commitment has been favored by immunologists although in other fields of biology, notably, neurobiology, plasticity has been acknowledged for long time. Only recently have immunologists turned their interests

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgments

We thank Diane Schad for her help in preparing the figures and M.L. Grossman for editorial help.

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Fine-tuning of T cell responses during infection

Introduction

Section snippets

Infection, inflammation and T cell immunity

The origin determines the outcome (Figure 1)

Outlook

References and recommended reading

Acknowledgments

Eur J Immunol

Cell

J Immunol

J Immunol

Immunity

J Immunol

Cell Host Microbe

Eur J Immunol

PLoS Pathog

J Immunol

J Immunol

Trends Mol Med

Proc Natl Acad Sci U S A

Nature

Eur J Immunol

Nature

The roles of TLRs, RLRs and NLRs in pathogen recognition

Int Immunol

Origin and physiological roles of inflammation

Nature

Inflammatory signals in dendritic cell activation and the induction of adaptive immunity

Immunol Rev

Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells

Nat Immunol

Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity

J Exp Med

Dendritic cell quiescence during systemic inflammation driven by LPS stimulation of radioresistant cells in vivo

J Exp Med

Approaching the asymptote? Evolution and revolution in immunology

Cold Spring Harb Symp Quant Biol

Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins

J Immunol

Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages

Nat Immunol

A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17

Nat Immunol

Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome

Nature

Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells

Nat Immunol

The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat

Nat Immunol

A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses

Nat Immunol

IL-21 and TGF-beta are required for differentiation of human T(H)17 cells

Nature

IL-17A produced by gammadelta T cells plays a critical role in innate immunity against listeria monocytogenes infection in the liver

J Immunol

Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma

Immunity

Function of Nod-like receptors in microbial recognition and host defense

Immunol Rev

Pattern recognition receptors in the immune response against dying cells

Curr Opin Immunol

Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells

J Biol Chem

Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells

Immunity

How microorganisms tip the balance between interleukin-12 family members

Nat Rev Immunol

Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway

Blood

Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17

Nat Immunol

Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells

Nat Immunol

Stage-specific sampling by pattern recognition receptors during Candida albicans phagocytosis

PLoS Pathog

Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity

Nat Med

Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells

J Exp Med