T Helper Cells

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

CD4 T cells make 60% of circulating T cells. CD4 T cells are cytokine-secreting helper cells. They recognize antigens only through MHC II -- the antigen has to be ingested and degraded by antigen-presenting cells (APC) and presented on the cell surface via MHC II molecules.


Schematic representation of MHC class II. Image source: Wikipedia.


MHC Class II Processing. This video describes the assembly of MHC Class II molecules. This video is from: Janeway's Immunobiology, 7th Edition, Murphy, Travers, & Walport. Source: Garland Science.

The CD4 molecule is a protein of the immunoglobulin superfamily. The HIV virus binds to CD4 via its gp120 and therefore is has a special predilection for infecting CD4 cells.


Diagram of HIV. Image source: Wikipedia.

CD4/CD8 ratio is a sensitive marker to predict HIV infection in infants. Shearer et al. analyzed HIV-exposed infants and found that a CD4/CD8 ratio of 1.8 or less at 3 months of age was more sensitive than CD4+ T-cell counts to predict HIV infection. This finding may be useful to help HIV diagnosis in poorer countries without access to virology laboratories.

Th1 and Th2 Cells

CD4 helpers are divided into Th1 and Th2 subsets. The differentiation into Th1 or Th2 is driven by cytokines (IL2, IL4) which upregulate STAT molecules (signal transducers and activators of transcription).

Th1

Th1 cells participate in cell-mediated immunity (delayed type hypersensitivity reactions and killing of intracellular
pathogens), autoimmune diseases (e.g. RA, MS).

Th2

Th2 cells participate in humoral immunity via activation of B cells. They play an important role in allergic inflammation (e.g. asthma, allergic rhinitis) via activation of mast cells andeosinophils. Th1/Th2 bias is a term which describes whether Th1 or Th2 response is predominant.

Th
I
Infection
Intracellular pathogens
Immune diseases, i.e. autoimmune diseases
Inflammatory bowel disease (IBD)

Th2
Antibodies, i.e. humoral immunity
Allergy
Asthma
Allergic rhinitis


Th1 and Th2 subsets (mind map)

Early childhood immunizations have been viewed as promoters of asthma by:

- stimulating a TH2-type immune response
- decreasing "microbial pressure," thus shifting the balance between TH1 and TH2 immunity

Number of CD4 T cells /mcL is different in children and adults

Adults, older than 18 years
More than 500

Children - depends on age

0-1 year
More than 1500

1-5 year
More than 1000

6-12 year
More than 500

The hygiene hypothesis

Decreased atopic sensitization associated with living in a farm was explored by studying bacteria found in cowsheds. Acinetobacter lwoffii and Lactococcus lactis shifted the immune response toward the secretion of TH1 cytokines in a murine model. One begins to wonder if biotherapy with bacterial extracts would be in the future of studies of allergy prevention.

T helper cells (click to enlarge the image).


Regulatory T cells - 6 groups have been described as of year 2010 (click to enlarge the image).

Published: 06/28/2010
Updated: 08/16/2010