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Th1/Th2 Signaling and HIV-1

bogleb aguldo at delphi.com
Mon Aug 14 03:40:06 EST 1995

13 August, 1995
	In regard to signaling the Th1/Th2 paradigm. . . .
	Reading an interview with Jay Levy by Mark Mascolini last week got me
thinking.  It seems to me that there is an extremely strong correlation
between Th1 and Th2 responses and class I and class II MHC antigens,
respectively.  I understand that both Th1 and Th2 cells must interact via
their CD4 molecules with class II MHC, while CD8+ cells interact via their
CD8 molecules with class I MHC.  But I also understand that while a Th1-type
response is favored by IL-12 via macrophage and NK cell, the initiating
trigger for a Th2-type response is less clear.
	Why not assume that the trigger for Th2 is plain old recognition of
exogenous antigen presented by class II MHC?  Th0 recognizes class II, Th0
matures to Th2, which favors Ab production against exogenous antigen.  In
this scenario, the primary role for Th0 is to go to Th2.  Th0 goes to Th1
only as a back-up plan in order to help support cell-mediated immunity.
	Perhaps there is an analogous CD8+ trigger.  Tc0 recognizes class I,
Tc0 matures to Tc1, which favors cell-mediated attack against endogenous
antigen.  The primary role for Tc0 is to go to Tc1.  Tc0 goes to Tc2 only
as a back-up plan in order to help support antibody production.
	Tc2 might be mutually promoting with Th2, and Tc1 might be mutually
promoting with Th1.  Thus, a Tc2 cell could "help" a Th2 response, just as a
Th1 cell could (indirectly?) promote a cell-mediated Tc1 response.  Depending
upon the pattern, both CD4+ and CD8+ cells could be sometimes helpers, some-
times suppressors.
	A specific problem:  HIV-1 infection.  The Th1 to Th2 conversion is
considered a poor prognostic indication.  But which is cart and which is
horse?  Might not class I present intracellular virus and class II present
phagocytosed extracellular virus?  Might the Th1 to Th2 conversion represent
increased relative intracellular to extracellular viral load?  If so,
shifting the balance back to Th1 might focus the immune system on infected
cells when the bigger problem is extracellular virus.
Bob R. Bogle, MT(ASCP),CLS(NCA)		Voice:   (520) 694-6107
Dept. Clinical Pathology		E-mail:  aguldo at delphi.com
HLA/Immunology Laboratories		The views expressed herein are my own
University Medical Center		and should in no way be construed to
1501 N. Campbell Avenue			represent those of U.M.C.
Tucson, AZ  85724					-- THE MANAGEMENT

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