Immunotechnology. 1998 Jan;3(4):233-44.

The TH1/TH2 paradigm in allergy.

Maggi E.
Source Clinical Immunology Dept., University of Firenze, Italy.

Abstract
Recent evidence has been accumulated to suggest that allergen-reactive type 2 helper T cells (Th2) play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, i.e. the cellular triad involved in the allergic inflammation. Interleukin (IL)-4 production by a still unknown cell type (T cell subset, mast cell/basophil?) at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a favoring role. In contrast, cytokines such as interferon (IFN-alpha, IFN-gamma, IL-12 and transforming growth factor (TGF)-beta, and hormones, play a negative regulatory role on the development of Th2 cells. However, the mechanisms underlying the preferential activation by environmental allergens of Th2 cells in atopic individuals still remain obscure. Some gene products selectively expressed in Th2 cells or selectively controlling the expression of IL-4 have recently been described. Moreover, cytokines and other gene products that dampen the production of IL-4, as well as the development and/or the function of Th2 cells, have been identified. These findings allow us to suggest that the up-regulation of genes controlling IL-4 expression and/or abnormalities of regulatory mechanisms of Th2 development and/or function may be responsible for Th2 responses against common environmental allergens in atopic people. The new insights in the pathophysiology of T cell responses in atopic diseases provide exciting opportunities for the development of novel immunotherapeutic strategies. They include the induction of nonresponsiveness in allergen-specific Th2 cells by allergen peptides or redirection of allergenspecific Th2 responses by Th1-inducing cytokines, altered peptide ligands, allergens incorporated into recombinant microorganisms or bound to appropriate adjuvants, and plasmid DNA vaccination. In severe atopic patients, the possibility of nonallergen-specific immunotherapeutic regimens designed to target Th2 cells or Th2-dependent effector molecules, such as specific IL-4 transcription factors, IL-4, IL-5 and IgE, may also be suggested.

BMJ 321 : 424 doi: 10.1136/bmj.321.7258.424 (Published 12 August 2000)

Paper

Th1 and Th2 responses: what are they?

Abi Berger

Affiliations 1. BMJ Cytokines are the hormonal messengers responsible for most of the biological effects in the immune system, such as cell mediated immunity and allergic type responses. Although they are numerous, cytokines can be functionally divided into two groups: those that are proinflammatory and those that are essentially antiinflammatory but that promote allergic responses. T lymphocytes are a major source of cytokines. These cells bear antigen specific receptors on their cell surface to allow recognition of foreign pathogens. They can also recognise normal tissue during episodes of autoimmune diseases. There are two main subsets of T lymphocytes, distinguished by the presence of cell surface molecules known as CD4 and CD8. T lymphocytes expressing CD4 are also known as helper T cells, and these are regarded as being the most prolific cytokine producers. This subset can be further subdivided into Th1 and Th2, and the cytokines they produce are known as Th1-type cytokines and Th2type cytokines. Th1-type cytokines tend to produce the proinflammatory responses responsible for killing intracellular parasites and for perpetuating autoimmune responses. Interferon gamma is the main Th1 cytokine. Excessive proinflammatory responses can lead to uncontrolled tissue damage, so there needs to be a mechanism to counteract this. The Th2-type cytokines include interleukins 4, 5, and 13, which are associated with the promotion of IgE and eosinophilic responses in atopy, and also interleukin-10, which has more of an anti-inflammatory response. In excess, Th2 responses will counteract the Th1 mediated microbicidal action. The optimal scenario would therefore seem to be that humans should produce a well balanced Th1 and Th2 response, suited to the immune challenge. Many researchers regard allergy as a Th2 weighted imbalance, and recently immunologists have been investigating ways to redirect allergic Th2 responses in favour of Th1 responses to try to reduce the incidence of atopy. Some groups have been looking at using high dose exposure to allergen to drive up the Th1 response in established disease,1 and other groups have been studying the use of mycobacterial vaccines in an attempt to drive a stronger Th1 response in early life.2 An additional strategy is being used to prevent the onset of disease; this involves the study of pregnancy and early postnatal life. Both of these states are chiefly viewed as Th2 phenomena (to reduce the risk of miscarriage, a strong Th2 response is necessary to modify the Th1 cellular response in utero). The fetus can switch on an immune response early in pregnancy, and because pregnancy is chiefly a Th2 situation, babies tend to be born with Th2 biased immune responses. These can be switched off rapidly postnatally under the influence of microbiological exposure or can be enhanced by early exposure to allergens. It is also hypothesised that those who go on to develop full blown allergies may be those who are born with a generally weaker Th1 response, although it is now apparent that babies with allergies produce weak Th1 and Th2 responses. Some people have suggested that immunisationprogrammes (and the subsequent reduction in microbiological exposure) are responsible for the increasing incidence of atopy. There is, however, no evidence that immunisation causes atopy. Moreover, this is not an argument that we should be exposing children to potentially fatal diseases again. If experiencing native diseases reduces the incidence of atopy, then the task of immunologists must be to develop vaccines that mimic the positive effects of infection.

+ Author

References
Gereda JE, Leung DYM, Thatayatikom A, Streib JE, Price MR, KlinnertMD, et al . Relationship between house dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet 2000;355:1680-1683. Jones CA, Holloway JA, Warner JO . Does atopic disease start in ffoetal life? Allergy 2000;55:2-10.

The helper T-cells (a type of T-lymphocyte) produce enormous amounts of two types of cytokines: Th1 and Th2. The Th1 cytokines produced by the helper T-cells produce a pro-inflammatory response; The TH2 cytokines produce an anti-inflammatory response, but promote allergic responses.

What Do the TH1 Cytokines Do?

The Th1-type cytokines produce inflammation to kill intracellular parasites (viruses and certain bacteria, such as Listeria and Mycobacterium tuberculosis the bacillus that causes TB). These cytokines also perpetuate any form of autoimmune response, and can cause cell-mediated allergies. Th1-type lymphokines are involved in the development of organ-specific autoimmune diseases, such as autoimmune uveitis, allergic encephalomyelitis, or insulin-dependent diabetes mellitus.

What Do the TH2 Cytokines Do?

The TH2 cytokines counteract the effects of the TH1 cytokines they have an anti-inflammatory action. But they also help kill extracellular pathogens (which live outside the bodys cells and are exposed to antibodies in blood and other body fluids). The TH2 cytokines induce a pronounced allergic response. If you suffer from IgE-mediated allergies, or asthma, you are likely to be over-producing TH2-types of cytokines, and have a TH2-weighted imbalance. Th2-cell predominance is found in patients with chronic graft-versus host disease, progressive systemic sclerosis, systemic lupus erythematosus, and allergic diseases.

Read more at Suite101: What are TH1 and Th2 Forms of Immune Response?: An Immune System
Out of Balance | Suite101.com http://www.suite101.com/content/what-are-th1-and-th2-forms-ofimmune-response-a118467#ixzz1R3GODD5q

Read more at Suite101: What are TH1 and Th2 Forms of Immune Response?: An Immune
System Out of Balance | Suite101.com http://www.suite101.com/content/what-are-th1-and-th2-formsof-immune-response-a118467#ixzz1R3GK5FoD