Opinions on whether TH1 and TH2 cell types originate from TH0

Chris Hodgson lsrbd at csv.warwick.ac.uk
Tue Mar 15 12:42:00 EST 1994

Dear Immunonetters,

I feel that this discussion warrants some clarification and further opinion.

I am in agreement with the recent article postees as regards the presence of
TH1 and TH2 cells during differing responses. My personal interest lies
within sensitization to chemical allergens, some of which can be classified
aas respiratory or contact dermatitis agents.

However the immune response at the TH cell level is not absolute to one or
the other committed cytokine-based cell types, rather both specific TH1 & TH2 
cells are formed during rounds of clonal expansion to an antigen (be this
microbial, oncogenically derived or allergen). 

The balance between specific TH1 and TH2 cells is altered according to the
antigen(s), the cell types and millieu in which they are presented and is
further likely to be mediated by a parallel clonal selection of B-cells with
lymph nodes local to the inflammatory site [i.e. a region from which antigen
is derived by APC, and which attracts specific T and B lymphocytes from the
circulating networks)

In essence I am saying that one or the other type of TH cell may predominate
at the antigenic site - this effect will be more markedly apparent during a
true amanestic memory response where memory cells rapidly commit to the
beginnings of inflammation. Good evidence exists for the role of TH1
specific cytokines in mediating delayed type hypersensitivity, and also for
TH2 cytokines in recruiting the cells types (eosinophils in particular)
associated with late-phase reaction in asthma. 

I would be interested to know if anyone is aware of what happens to a TH1 or
TH2 cell once infection has been curbed / erradicated. Do they fractionate
into populations as follows :

1) TH1 and/or TH2 cells, short lived and poised for blast formation
2) TH1 and/or TH2 cells, long lived memory cells (CD45 isoforms ?)
3) TH0 cell state - Can a TH1 or TH2 cell return to this and retain a memory
   phenotype thus having the potential to become either TH1 or TH2-like on
   future encounters with the same of similar antigen ?

It does not seem beyond credibility that all three of the above types of
population may result following "recovery". I think it likely that in
recurrent asthmatics and eczema sufferers that frequent exposure to
allergens never gives the TH2-like cells responding any opportunity to
diminish at reactive inflammatory sites - this might futher be maintained by
B-cell IgE production which is just ticking over and longer term antigen
presentation both at previously damaged tissue regions and within regional
lymph nodes.

I certainly feel that the TH1 / TH2 phenotype are the extremes of TH cell
development and are only readily observable during an ongoing immune
response. I begin to view them more as a product of short-term
immunoevolution within mammals, recruiting different effector cells and
inducing appropriate killing mechanisms (e.g DTH is essential for virally
infected cell erradication).

Finally, in what has been a long post (my apologies), I do not see any
problems in the manner in which we classify TH1/TH2 like cells based on their
cytokine-production potential. From tissue biopsies most workers approach
the analysis by mRNA in-situ hybridisation, in vivo cultures can
demsonstrate secretion patterns of clones or mixed cells. 

I encourage and welcome further discussion from all of the newsgroup readers
on this thread - TH1 and TH2 cells are pivotol to the effector phase of
immune respones and are here to stay.

Chris Hodgson

Chris Hodgson             \Where all roads lead to mystery
University of Warwick      \Serendipity will be found
Coventry, U.K.              \--<MiCrObE..MaNiAc>-94--
+44 203 523523 Ext. 2568     \lsrbd at csv.warwick.ac.uk

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