From: bigoldberg@igc.apc.org (Billi Goldberg)
Newsgroups: sci.med.aids
Subject: TH1/TH2 and HIV/AIDS
Date: 11 Jan 93 07:19:06 GMT
Organization: unspecified
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6743


                        TH1/TH2 AND HIV/AIDS

The following is excerpted by from "T Helper Cell Immune Dysfunction 
in Asymptomatic, HIV-1-Seropositive Individuals: The Role of TH1-TH2 
Cross-Regulation" by Gene M. Shearer and Mario Clerici of the 
Experimental Immunology Branch, National Cancer Institute, National 
Institutes of Health, Bethesda, Md. USA.

The chapter is included in "Regulation and Functional Significance of 
T-Cell Subsets" edited by Robert L. Coffman and published in 1992 by 
Karger. It is Volume 54 of the Chemical Immunology series.

Page 32-35:

(1) HIV-specific TH1 responses are immunoprotective and prevent 
infection, and/or keep the infection under control. Limiting amounts of 
HIV-1 that induce T-cell immunity but not antibody production are 
characteristic of this phase.

(2) HIV seroconversion represents a state in which the viral replication 
has increased and has generated enough antigen to activate TH2 responses 
and HIV-specific antibodies. Although antibodies provide some immune 
protection, a state of seropositivity is ultimately indicative of the 
failure of the immune system to keep the virus in check.

(3) An individual can be in a 'predominant TH1' (TH1>TH2) or a 
'predominant TH2' (TH2>TH1) state, depending on exposure to recent 
immunologic stimuli that may be unrelated to HIV-1 infection.

(4) An individual in a TH1 state is more resistant to HIV-1 infection 
and/or AIDS progression than an individual who is in a TH2 state, 
possible due to unrelated immunologic events that promote a TH1-to-TH2 
switch.

(5) IL-10 is an important cytokine in the regulation of resistance and 
susceptibility to HIV-1 infection and/or progression to AIDS, and 
increases in IL-10 will be predictive for a more susceptible state. Any 
non-HIV infection or immune stimulus that enhances IL-10 production will 
increase susceptibility for infection or AIDS progression."

...

"If IL-10 controlled TH1-TH2 cross-regulation is important in resistance 
and susceptibility to HIV-1 infection and/or AIDS progression, 
consideration should be given to the possibility of immune-based 
therapy that would be designed to maintain an individual in a 
predominant TH1 state, and to convert an infected or at-risk individual 
who is in a predominant TH2 state to a predominant TH1 state. 
Furthermore, AIDS vaccine programs should take into consideration 
TH1-TH2 cross-regulation. This could be important both for the HIV-1 
antigenic determinants used to immunize and the adjuvant employed. For 
example, in mice some antigenic determinants of L. major induce TH1 
responses, whereas others can induce TH2 responses. Thus, one might 
want to consider HIV-1 subunit vaccines that would primarily induce 
cell-mediated rather than humoral immunity. This is different than the 
criteria now being used to evaluate candidate AIDS vaccines, which are 
either anti-HIV antibody production only or stimulation of both humoral 
and cellular immunity. Furthermore, certain adjuvants are primarily TH1 
stimulators, whereas others can be TH2 activators. Alum, the adjuvant 
currently used in AIDS vaccine trials, predominantly activates TH2 
responses in mice, whereas BCG is a potent TH1 adjuvant."

"If our model is correct, AIDS researchers may have been studying the 
immunologic failures of HIV-1 infection for the past decade 
(seropositive individuals), and ignoring what may be the immunologic 
successes of HIV-1 exposure (exposed seronegative individuals who 
exhibit evidence of TH immunity to HIV antigens). Investigators in AIDS 
research need to become more familiar not only with the cytokines that 
regulate HIV-1 infection, but also with those that regulate T helper 
cell immunity. Based on the findings summarized in this article, we 
consider that IL-10 and possibly other cytokines that regulate TH1-TH2 
cross-regulation will be important factors for controlling the AIDS 
epidemic, particularly during the early phases of exposure and 
infection"
Newsgroups: sci.med.aids