IL-2 interesting finding

Ken Frauwirth frauwirt at mendel.Berkeley.EDU
Mon Dec 6 20:06:13 EST 1993

In article <2e066bINNsoh at dns1.NMSU.Edu>, smori at nmsu.edu (Shahram Mori) writes:
|> Dear netters,
|> I read in a recent Science article, that IL-2 deficient mice had normal
|> CD4 and CD8 responses while their NK cells activity was drastically reduced.
|> I was very surprised. IL-2 is supposed to be an important factor in the
|> differentiation of T-cells. There has been suggestions ( By Jonas Salk and
|> Peter Bretscher) that a switch in Th-1 to Th-2 is the reason for
|> progression of HIV to AIDS. If IL-2 deficient mice can have normal CMI, then
|> what is it that induces the differentiation of T-cells. How does this
|> affect the idea about Th1 switch to Th2.
|> I would like to hear your ideas on this matter.
|> cheers
|> Shahram
|> e-mai smori at nmsu.edu

What seems to be very likely (especially based on similar results of
other cytokine knock-outs) is that many of the cytokines have
overlapping, if not completely redundant, functions.  Also, according to
a recent seminar here by Anne O'Gara of DNAX:

1) IL-12 + gamma-IFN will induce CD4+ cells to differentiate into a Th-1
   phenotype in vitro, when also supplied with antigen and APC (D.C.'s, 
   which do not induce differentiation without added cytokines).
2) Anti-IL-4 will *also* induce differentiation to Th-1 phenotype, but
   apparently by a different mechanism (IL-12/IFN + anti-IL-4 gives an
   additive effect).

Since there may be more than one mechanism of inducing Th-1 phenotype,
the loss of one mechanism may not have much visible effect on the mice
under the conditions tested.  However, it is also important to remember
that all of these knockout mice live in antiseptic environments and are
tested under very defined conditions.  It is not unlikely that defects
would become evident under the stresses of normal (i.e. non-laboratory)

Ken Frauwirth                  BBB   IIIII    OO    K  K   EEEEE   N   N
frauwirt at mendel.berkeley.edu   B  B    I     O  O   K K    E       NN  N
Dept. of Molec. & Cell Bio.    BBB     I     O  O   KK     EEEE    N N N
Immunology Division            B  B    I     O  O   K K    E       N  NN
Univ. of Cal., Berkeley        BBB   IIIII    OO    K  K   EEEEE   N   N 

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