TH1 vs. TH2 Redux

iddavis at vms.cis.pitt.edu iddavis at vms.cis.pitt.edu
Wed Jul 26 10:37:06 EST 1995


In article <xtGDR4k.aguldo at delphi.com>, bogleb <aguldo at delphi.com> writes:
> 	(1) At what point does a CD4+ cell commit to a TH1 vs. a TH2
> response?  Does it "commit," or is the process reversible?

This is still a bit of an open question, but there was an interesting article
a few weeks ago (and do you think I can remember the journal?) looking at
Th1/Th2 commitment in BALB/c mice (which tend to mount Th2 responses rather
than Th1), using BALB/c-derived T-cells transgenic for a TCR specific for a
particular antigen.  It was shown that in that experimental situation, 
commitment to Th2 phenotype was irreversible although Th1 cells could be 
induced to change to a more Th2 phenotype.  Unfortunately only BALB/c 
T-cells were studied so we still don't know if this is a general finding or 
if it is something peculiar to BALB/c mice (which behave oddly, see above).

> 	(2) When I took an intro immunology course way back in '90 or so,
> I remember learning that class I MHC presents endogenous self or tumor/viral
> peptides, which are recognized by TCR of CD8+ cell, which then is cytotoxic
> to the APC and other cells with the same antigen (to oversimplify to a
> ridiculous degree).  Where does the CD4+ cell involved in a TH1 response
> fit in to this scheme?  Do both the CD4+ cell and the cytotoxic CD8+ cell
> have TCR that recognize the foreign antigen?

Both have TCR.  To greatly simplify matters, the CD4+ Th recognizes antigen
in association with class II MHC.  It then provides help for the 
differentiation and function of other effectors, whether they be CTL (in
a Th1-type response) or B-cells (in a Th2 humoral-type response).  Exactly
which type of response is favored probably depends on a host of factors,
some of which include the initial cytokine milieu, or the exact stimulus
and the exact host type.  The initial presence of IL-12 tends to favor
Th1 responses, and the initial presence of IL-4 (perhaps made by an odd
CD4+NK1.1+ cell) tends to favor Th2 responses.  I am sure others will
correct me if this overdoes it!

Hope this is helpful.  It works for my simple mind.


Ian Davis				     iddavis at vms.cis.pitt.edu
University of Pittsburgh Cancer Institute



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