CD4 specific CTLs and Tolerance

James Kennedy jrken at ix.netcom.com
Thu Aug 24 11:31:45 EST 1995


In the posting of Aug. 19 (CD4 Tolerance and HIV) a concept of
naturally occurring peripheral tolerance for the CD4 molecule was
introduced. The presence of HIV in the system was postulated to cause a
breakdown of this tolerance with a shift toward increased CD4
lymphocyte destruction. This posting addresses the role which  CD4
specific CTLs play in this process.

CD4 specific CTLs may be the idiotypic effectors in this tolerance
network and they may also be responsible for the eventual  decimation
of their CD4 targets when HIV is present.   Zarling A. [J. of
Immunology, (1990) 144, 2992-2998] found such cells in HIV infected
humans which attacked non-HIV infected CD4 cells.  She also searched
for these CTLs in HIV infected chimpanzees but found none.  This would
seem to be a  pertinent finding as chimpanzees do not become immune
deficient when they are HIV infected.

Grant M. [J. Acquired Immune Defic. Syndr.,(1994), 7/6, 571-579] found
non-HLA restricted CTL in HIV+ subjects which killed activated
uninfected CD4+ lymphocytes. Evaluating HIV+ subjects, they found a
mean decrease in the CD4+ lymphocyte counts of +/- 36% over a 6 month
period when autologous CD4 specific CTLs were present .  In HIV
infected individuals without such CD4 specific CTL there was no
significant decrease in the mean CD4 count in the same period of time.



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