Why does the lack of HST lead to AIDS?

Why does the lack of HST result in the loss of systemic immune responses leading to AIDS?

This is the very fundamental immunological question of HIV pathogenesis and answering this will provide theoretical foundation for developing an effective vaccine against HIV.  If one assumes HST as just one type of effector memory T cells, as currently being regarded, the correct answer would not be achieved.  It has been the case until now.  In my previous post, I defined the HST as CD4 T cells that are susceptible for CCR5 (R5)-tropic HIV.  Accumulating data obtained from both with individuals infected with HIV and with non-human primates infected with SIV, support that the lack of HST will lead to AIDS and providing HST will cure AIDS, even though we need more cases on curing AIDS by providing HST with homozygous CCR5 mutation.  Nevertheless, it is a dramatic and breathtaking positive result (A German-Patient case).  Likewise, sparing HST from experimental SIV infection do not lead to AIDS like syndrome in non-human primates (similar to HIV in human, SIV depletes HST in pathogenic infection, but in non-pathogenic infection).  (many thanks to Dr. Guido Silverstri for his contribution on this part, http://www.yerkes.emory.edu/research/divisions/microbiology_immunology/silvestri_guido.html)

From now on, I will share my theory that are different from current immunological paradigms in several ways.  The crux of my theory is that HST are different but unique type of T cells from the rest of T cells (non-HST) in several ways.  Considering the HST as one of many T cells will create a major obstacle to solving problems of HIV infection and AIDS.

The following segment may require advanced-level of immunological knowledge with cutting edge (up to date) immunology information.  If you have any question, pleasae do not hesitate contact me. I will do my best to explain them.

1. HST could be the source for a variety of effector T cells.  

If that were the real case, the loss of HST by HIV infection will result in deficiency in systemic immune responses, but not just an antigen specific T cell response.  This hypothesis is supported by numerous reports.  It has been shown that HIV infected individuals lose Th17 cells, lose of B cell function possibly due to the lack of follicular helper T cells, and also lose secretion of IFN-g at an early stage.  

2. HST could be the T cells that can exclusively activate antigen presenting cells.  This hypothesis is deviation from a current immunological paradigm but makes perfect sense, since activation of an antigen specific T cells require professional antigen presenting cells that were preactivated.  This hypothesis is supported by a work of Sallusto’s group published in JEM. It is possible that effector memory T cells that they were referred in that paper could be the HST.  HST and effector memory T cells share many similarities.  If this will be the real case, HST could be a specific T cells that can activate antigen presenting cells by exclusively expressing CD40L.
3. HST can become polyfunctional effector T cells.  Polyfunctionality of T cells are considered as T cells that are missing in HIV infected individuals and AIDS patient.  Therefore, the generation of polyfunctional T cells has been used to gauge the HIV vaccine efficacy.  However, it cannot be simulated a condition where HST are missing by HIV infection, this current method of examining vaccine efficacy may not be an ideal method.
4. HST could proliferate much faster than non-HST.  This hypothesis is based on my personal instinct and observation made by a group of Silvestri.  It means that HST could be an early sentinels at the gut and other mucosal effector sites.  Therefore, the lack of these HST could open the door for the subsequent fall of protective immunity as seen in AIDS patient.  There is a strong possibility that HST could be T cells that are involved in innate immune responses, instead of adaptive cell mediated immunity.
5. HST could be the TRM, effector memory T cells reside in mucosal effector sites. Effector T cells found in mucosal effector sites had been considered for a,long period of time that they were moved to the site and a specific environment made TRM with their distinct phenotypes. With recent correction by the same group of investigator (Masopust's), it should be considered that TRM are different from other memory T cells found in lymphoid tissue.

I will expand this later

October 17th 2012