JC July: IL12 and HIV

FORSDYKE at QUCDN.QueensU.CA FORSDYKE at QUCDN.QueensU.CA
Thu Jul 21 12:40:49 EST 1994


   Dr. Mori asked me to post the following:      Don Forsdyke

Shahram Mori                                       _/\_
Program in Molecular Biology                      _\  /_
Dept. of chemistry and Biochemistry Box 3C        \_  _/
NMSU  Las Cruces NM                                 ||
88003



---------- Forwarded message ----------
Date: Wed, 20 Jul 94 19:15:11 EDT
From: Anton Scott Goustin <asg at cmb.biosci.wayne.edu>
To: Shahram Mori <smori at nmsu.edu>
Subject: Re: JC July, 1994 - IL12 and HIV


DEAR DON, I GOT THIS FROM ANTON. CAN YOU POST THIS ARTICLE IN OUR
DISCUSSION OF IMMUNOLOGY GROUP? I DON'T KNOW HOW TO POST FROM MY E-MAIL
DIRECTLY ON THE NET.Thanks a mil. :(



In article <30adu3$kiq at dns1.NMSU.Edu> you wrote:
u also might wish to check out a paper by Romagnani in AIDS Research and Human
Retroviruses:
Romagnani S, Maggi E, Del Prete G. 1994. An alternative view of the
Th1/Th2 switch hypothesis in HIV infection. AIDS Res Hum
Retro;10(5):iii-ix.

Abstract: A theory that seeks to explain what induces the relentless
progression of HIV-infection subjects to AIDS has received considerable
attention. This theory holds that HIV infection results in a Th1/Th2
switch. However, analysis of constitutive cytokine mRNA expression in
lymphoid tissues from HIV-infected individuals did not confirm an in
vivo Th1/Th2 switch. Moreover, data available at the level of in
vitro-stimulated peripheral blood mononuclear cells or cloned T cells do
not provide clear evidence for a definite switch to the Th2 responses in
any HIV-infected subject and in any phase of HIV infection. At most,
currently available data on the profile of cytokines released in
response to in vitro stimulation suggest a Th1-to-Th0 shift in a
proportion of memory CD4+ T cells. On the other hand, experiments of in
vitro infection with HIV of already established CD4+ T cell clones
indicated that Th2 and Th0 support HIV replication better than Th1
cells, suggesting that early destruction of Th2 cells by direct or
indirect HIV-mediated cell killing may occur. Finally, in some
HIV-infected individuals with low CD4+ T cell counts, a prevalence of
CD8+ T cells producing type 2 cytokines was found in both peripheral
blood and skin. Thus, although the induction of a general Th2 state in
HIV infection is not proven, enhanced production of type 2 cytokines may
occur in a proportion of HIV-infected individuals and play some role in
the pathogenesis of the disease.

from Anton Scott Goustin <asg at cmb.biosci.wayne.edu>
: J Matthew Buchanan (jbuchana at magnus.acs.ohio-state.edu) wrote:


: : The loss of IL-12 production in the PBMC and not in lymphoid organ cells may
be
: : due to the current locale of the HIV.  There is thought that the HIV
localizes
: : itself during stages of infection, going from a high viremia to a 'hiding'
: : state in the lymph organs.  It would be in teresting to see if the loss of
: : IL-12 production follows the virus during a time-course study.

: : The idea that distant cells could make up for the local IL-12 producito loss
: : ignores the idea that cytokines acive some specificity by acitng over only
very
: : short distances.  Thus, distant IL-12 probably remains just that, distant.
A
: : local loss of IL-12 would have a local loss of TH1 and CMI, not systemic.
: : Possibly, this would become systemic over time, however, if enough local
: : wipeouts occured.

: Matt, but if  enough IL-12 production is achieved in the Lymphoid
: tissues, as the authors seem to be hinting then there are Th1 induction and NK
: stimulation which can differentiate and proliferate and reach other sites
: in the body. True that the action of Cytokines is short-distanced but the
: primed cells " circulation" is not.


: : In the latest Science, Fauci and another group present papers stating that
they
: : did not observe a loss in TH1 profiles.  Il-12 was not addressed (at least
not
: : noticed in my first skim!).  Gets more and more confusing all the time....

: : The quest marches on.....


: This is amazing. This finding is in Direct contradiction to Dr Jonas Salk
: and Dr Peter Bretscher ( my Good old immunology professor back in
: Saskatchewan) who showed evidence that as asymptomatic HIV-seropositive
: individuals progress towards AIDS , there is a shift from Th1-mediated
: cytokine production to a Th2-mediated one( Science Vol260:1270 28 may 1993).
:  This would have correlated with
: the decrease in IL-12 production as the Predomninace of Th2-mediated
: cytokines produces IL-10 which is a -ve regulator of IL-12.
: I am gonna get a hold of last week's Science.

: When will these confusing findings stop? when you get all excited about an
: aspect of immunology of HIV, there comes a study to contradict it.
:  :Matt
: : MBUCHANAN at opus.mco.edu

: Cheers.
: --
: Shahram Mori                                     _/\_
: Program in Molecular Biology                    _\  /_
: Dept. of chemistry and Biochemistry Box 3C      \_  _/
: NMSU  Las Cruces NM                               ||





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