Genetic Analysis of Cytokine Promoters in Nonhuman Primates: Implications for Th1/Th2 Profile Characteristics and SIV Disease Pathogenesis
The shift from a predominant synthesis of prototype Th1 cytokines to Th2 or Th0 type of cytokines by antigen activated PBMC's from HIV infected humans and SIV infected disease susceptible rhesus maca...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2004-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1080/10446670410001670472 |
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| Summary: | The shift from a predominant synthesis of prototype
Th1 cytokines to Th2 or Th0 type of cytokines by antigen
activated PBMC's from HIV infected humans and SIV infected
disease susceptible rhesus macaques (RM) has been shown to
be associated with disease progression. Paradoxically, antigen
activated PBMC's from sooty mangabeys (SM), which are naturally
infected with SIV and are disease resistant despite high viral loads,
maintain a predominant Th2 cytokine profile. It has been reasoned
that the resistance to perturbations of cytokine synthesis by slow
and/or nonprogressor HIV infected patients and SIV infected disease
susceptible RM is secondary to inherited polymorphisms within
the promoter regions for cytokines. Similar promoter polymorphisms
could also contribute to the cytokine profile of PBMC's from SM. To
address this issue promoter regions for the major Th1/Th2 cytokines
from RM and SM were cloned and sequenced. Sequence analysis
of promoter fragments of IL-4, IL-10, IL-12 p40, IFN-gamma and
TNF-alpha from the two monkey species showed varying degree of
homology ranging from high degree of homology detected for
IFN-gamma promoter (>99%) to relatively high degree of polymorphism
detected for TNF-alpha promoter (94% homology). In addition, several
variable regions within the promoters of IL-12 p40, IL-10 and
TNF-alpha in the two species contain polymorphisms in sequences
that constitute binding sites of known transcription factors (TF). Such
differences are likely to differentially bind TF and thus either
qualitatively and/or quantitatively affect the regulation of cytokine
synthesis in these two species and potentially
contribute to disease progression and/or resistance. |
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| ISSN: | 1740-2522 1740-2530 |