From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: DC, CMI and DTH
Note: non-commercial reproduction.
Archive-Number: 5796
Organization: UCLA, Computer Science Department
Date: Tue, 28 Jul 92 08:30:34 PDT

The world of AIDS is getting more and more interesting.  Dendritic cells 
and the cell mediated immune response *seem* to be involved in AIDS.

(These excerpts have been posted before, but were included with other
stuff.)

From the CDC Summary of 7/28/92
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"Dendritic Cells Exposed to Human Immunodeficiency Virus Type-1  
Transmit a Vigorous Cytopathic Infection to CD4 T Cells" Science 
(07/17/92) Vol.257, No.5068, P.383 (Cameron, Paul U. et al.)
     Dendritic cells can act as a catalyst in the transmission of a  
cytopathic infection like HIV, according to Paul U. Cameron and  
colleagues at Rockefeller University in New York, N.Y.  The  scarcity of 
infected CD4 cells in HIV-positive patients contrasts with the greatly 
reduced numbers and function of these  lymphocytes.  A pathway is 
described in which dendritic cells  carry HIV to uninfected T cells, 
amplifying the cytopathic  effects of small amounts of virus.  After 
exposure to HIV-1,  dendritic cells continue to present superantigens 
and antigens,  forming clusters with T cells that are driven to 
replicate.   Infection of the dendritic cells cannot be detected, but 
the  clustered T cells form syncytia, release virions, and die.   
Mucosal and airway dendritic cells may carry and present HIV to  
responding T cells at the same time as the T cells are activated  by 
other environmental antigens carried by dendritic cells.   Dendritic 
cells that carry HIV-1 may facilitate the lysis and  loss of antigen 
specific CD4 T cells in AIDS.  Transmission  through dendritic cells is 
more efficient than through other  antigen-presenting cells.  This may 
be due to the potency of  dendritic cells in activating large numbers of 
CD4 T cells, the  researchers conclude. 
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From the Amsterday Conference Newsletter 7/22/92

Salk reveals dramatic new vaccine theory  
by Sharon Kingman 

His theory relies on the observation that the first reaction of the  
immune system after infection is among its T cells. This cell-mediated 
immunity is called the TH1 response. An example is the reaction known as 
delayed type hypersensitivity, when a red wheal appears on the skin 
following injection of an antigen. As time after infection increases, 
the other "arm" of the immune system swings into action, with the 
production of antibodies. This humoral immunity is called the TH2 
response.   Salk quotes a study by Bretscher and colleagues in support 
of this theory. These researchers injected one group of mice with a 
small dose of the organism that causes leishmaniasis and a second group 
with a large dose. The first group had a good delayed type 
hypersensitivity reaction while the second group had a stronger antibody 
response. When challenged with the infectious agent,  
however, only the animals in the first group resisted infection. Other 
researchers, led by Bloom, have shown that in patients with  
leprosy, relative resistance to the disease is associated with cell- 
mediated immunity, while those who produce antibodies are highly  
susceptible.  

Work by Gene Shearer and his colleague at the National Institutes of  
Health in the US backs up the theory. Shearer found that individuals who 
remained HIV-negative when tested with the highly sensitive polymerase 
chain reaction for HIV - despite having been at high risk of HIV 
infection - had good cell-mediated responses against HIV while remaining 
antibody negative.  

Skin reaction 

Salk has also looked at a cohort of HIV-positive patients who received 
his candidate vaccine based on inactivated HIV. About half of them had a 
local skin reaction when vaccinated, indicating a delayed type 
hypersensitivity reaction. This group has done much better clinically 
than the patients who did not respond in this way. Salk, who now works 
at the Salk Institute in La Jolla, California, says these data, taken 
together, suggest that the way to make a vaccine against HIV is to 
induce a cell-mediated response with an extremely small dose - probably 
measured in microgrammes.  Vaccines that induce neutralising antibodies 
are directed against cell-free viruses. But HIV is different, similar to 
an intracellular parasite. 
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Newsgroups: sci.med.aids