Wednesday, April 11, 2012

Lacking HST leads to AIDS and providing HST cures AIDS.

Lacking *HST leads to AIDS and providing HST cures AIDS.  
What and how can it be simpler than this?

(http://www.youtube.com/watch?v=A44LyMpnnmU).

*HST (CD4 T cells that are susceptible to CCR5 (R5)-tropic HIV).

It is now clear that *HST, CCR5+ CD4 T cells (also called Effector memory T cells: TEM), mainly reside in the gut mucosal area and other effector sites are the first targets for R5- tropic HIV infection and are depleted within a few days after infection.  The lack of the HST is the main cause for the ensuing pathogenesis mediated by HIV infection leading to AIDS.  It has been shown that providing CD4 T cells with a mutant form of CCR5 (CCR5delta32) can cure AIDS, as shown in a Berlin patient (a patient from New Jersey treated in Berlin, Germany) by bone marrow transplant (http://bloodjournal.hematologylibrary.org/content/117/10/2791.full) (http://www.youtube.com/watch?v=A44LyMpnnmU).  The patient had suffered not only from AIDS, but also from leukemia.  To cure leukemia (and AIDS as secondary), he was treated with bone marrow stem cell (BMSC) transplantation.  Donor BMSC contains a homozygous mutation of CCR5 (CCR5delta32), which prevents them from being infected by R5-tropic HIV.  Donor derived cells not only expanded, but also reconstituted recipient’s immune system.  It also showed that CD4 T cells were able to express CXCR4, another co-receptor for HIV.  Presence of CXCR4 expressing CD4 T cells did not affect the outcome of disease, suggesting the presence of CXCR4 (X4)-tropic HIV virus may not be as critical as R5-tropic HIV in inducing AIDS.  This clinical outcome provides one of the most compelling evidence that saving HST should be an ultimate goal for the HIV vaccine, since providing HST was able to reconstitute the mucosal immune system and cured AIDS.  However, it may require more than one clinical case to be generalized, to be sure.  

We need in depth knowledge of HST even before trying out extensive and expensive HIV vaccine trials.  Underlying scientific basis for almost all current HIV vaccine trials are in essence similar to those for smallpox vaccine or influenza vaccine.  Vaccination has been usually successful in most cases, with an exception of HIV and AIDS.  One clear difference between HIV and other pathogens are their target cells. HIV attacks and destroys HST while others not.  

Lacking HST leads to AIDS and providing HST cures AIDS.  
What and how can it be simpler than this?

This is my current hypothesis why the loss of HST could be the main reason for breaking down of systemic immune responses which eventually leads to AIDS.  It is not a breakdown of an antigen specific immune responses.  

To prove this hypothesis, it would require reevaluation of current understanding of immunological knowledge (paradigm) to interpret abundant information (data) gathered from HIV infected individuals or from SIV infected non-human primates.  I will explain those issues in other section.

Key words:
HST, AIDS, HIV, AIDS vaccine, CCR5, Berlin patient, bone marrow transplant, stem cells, CXCR4, CXCR4-tropic HIV,

I will update this with adding scientific papers, figures and better words. Any idea would be greatly appreciated if you can help (correct) me to expand this.

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