TH1 vs. TH2 Redux

M. Doherty M_Doherty at NIH.gov
Mon Jul 31 12:12:39 EST 1995


In article <xtGDR4k.aguldo at delphi.com>, bogleb <aguldo at delphi.com> wrote:

>  
>         A couple more very general questions.
>         (1) At what point does a CD4+ cell commit to a TH1 vs. a TH2
> response?  Does it "commit," or is the process reversible?

A controversial issue right now.  Consensus opinion would seem to be that
Th cells do commit, but that under some circumstances they can be
temporarily diverted to make a broader range of cytokines.  The commitment
process seems to occur fairly soon after activation, but no-one I know
will venture a solid opinion on exactly when.

>         (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?

Th cells fit into the scheme currently (it could change any time) as
modulators via the cytokines they express.  IFN-gamma increases class I
expression and various co-stimulatory molecules, IL-2 and IFN help
activate CD8 cells etc, while other cytokines further modulate effects. 
Just to complicate things, CD8 cells also seem to come in at least two
flavours (Tim Mosmann's terms Tc1 and Tc2 seem to be catching on) split
along the same lines as CD4 Th1 and Th2.  There is also some debate as to
whether all these different CD8 types are cytotoxic.
And yes, both CD4 and CD8 must be triggered through antigen-binding to the
TCR (at least under normal circumstances).  However, given that they see
the antigen in the context of different MHC molecules, it is unlikely that
they recognise the same epitopes.

Cheers, Mark



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