Abstract
Viremic slow progressors (VSP) are a rare subset of HIV-infected persons who exhibit slow immunologic progression despite high viremia. The mechanisms associated with this slow progression remain to be defined. Clinical characteristics of VSP are similar to those of natural hosts for simian immunodeficiency virus (SIV), such as sooty mangabeys (SM) and African green monkeys (AGM), who maintain near-normal CD4 counts despite high-level viremia but maintain low immune activation. Immune activation is a powerful predictor of disease progression, and we hypothesized that low immune activation might also explain the VSP phenotype. Using multiparameter flow cytometry, we assessed levels of T cell activation and regulatory T cells (Treg) in blood and rectal mucosa of VSP, typical progressors, virologic controllers, and seronegative controls. We also assessed Treg function and CD4 T cell proliferative capacity in VSP. Contrary to expectations, we found that VSP subjects have high levels of T cell activation in the gastrointestinal mucosa. The ratio of Treg to CD3 + T cells in the mucosa of VSP was relatively low, potentially contributing to increased immune activation. Nonetheless, CD4 +CD25- T cells isolated from these individuals displayed a comparatively weak proliferative response to anti-CD3 stimulation. These data reveal that the VSP phenotype is associated with elevated markers of mucosal immune activation and low numbers of mucosal Treg, suggesting that factors other than immune activation account for this phenotype.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 172-177 |
| Number of pages | 6 |
| Journal | AIDS Research and Human Retroviruses |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2013 |
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ASJC Scopus subject areas
- Immunology
- Virology
- Infectious Diseases
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Short communication : HIV+ viremic slow progressors maintain low regulatory t cell numbers in rectal mucosa but exhibit high t cell activation. / Shaw, Julia M.; Hunt, Peter W.; Critchfield, J. William; McConnell, Delandy H.; Garcia, Juan Carlos; Pollard, Richard B; Somsouk, Ma; Deeks, Steven G.; Shacklett, Barbara.
In: AIDS Research and Human Retroviruses, Vol. 29, No. 1, 01.01.2013, p. 172-177.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Short communication
T2 - HIV+ viremic slow progressors maintain low regulatory t cell numbers in rectal mucosa but exhibit high t cell activation
AU - Shaw, Julia M.
AU - Hunt, Peter W.
AU - Critchfield, J. William
AU - McConnell, Delandy H.
AU - Garcia, Juan Carlos
AU - Pollard, Richard B
AU - Somsouk, Ma
AU - Deeks, Steven G.
AU - Shacklett, Barbara
PY - 2013/1/1
Y1 - 2013/1/1
N2 - Viremic slow progressors (VSP) are a rare subset of HIV-infected persons who exhibit slow immunologic progression despite high viremia. The mechanisms associated with this slow progression remain to be defined. Clinical characteristics of VSP are similar to those of natural hosts for simian immunodeficiency virus (SIV), such as sooty mangabeys (SM) and African green monkeys (AGM), who maintain near-normal CD4 counts despite high-level viremia but maintain low immune activation. Immune activation is a powerful predictor of disease progression, and we hypothesized that low immune activation might also explain the VSP phenotype. Using multiparameter flow cytometry, we assessed levels of T cell activation and regulatory T cells (Treg) in blood and rectal mucosa of VSP, typical progressors, virologic controllers, and seronegative controls. We also assessed Treg function and CD4 T cell proliferative capacity in VSP. Contrary to expectations, we found that VSP subjects have high levels of T cell activation in the gastrointestinal mucosa. The ratio of Treg to CD3 + T cells in the mucosa of VSP was relatively low, potentially contributing to increased immune activation. Nonetheless, CD4 +CD25- T cells isolated from these individuals displayed a comparatively weak proliferative response to anti-CD3 stimulation. These data reveal that the VSP phenotype is associated with elevated markers of mucosal immune activation and low numbers of mucosal Treg, suggesting that factors other than immune activation account for this phenotype.
AB - Viremic slow progressors (VSP) are a rare subset of HIV-infected persons who exhibit slow immunologic progression despite high viremia. The mechanisms associated with this slow progression remain to be defined. Clinical characteristics of VSP are similar to those of natural hosts for simian immunodeficiency virus (SIV), such as sooty mangabeys (SM) and African green monkeys (AGM), who maintain near-normal CD4 counts despite high-level viremia but maintain low immune activation. Immune activation is a powerful predictor of disease progression, and we hypothesized that low immune activation might also explain the VSP phenotype. Using multiparameter flow cytometry, we assessed levels of T cell activation and regulatory T cells (Treg) in blood and rectal mucosa of VSP, typical progressors, virologic controllers, and seronegative controls. We also assessed Treg function and CD4 T cell proliferative capacity in VSP. Contrary to expectations, we found that VSP subjects have high levels of T cell activation in the gastrointestinal mucosa. The ratio of Treg to CD3 + T cells in the mucosa of VSP was relatively low, potentially contributing to increased immune activation. Nonetheless, CD4 +CD25- T cells isolated from these individuals displayed a comparatively weak proliferative response to anti-CD3 stimulation. These data reveal that the VSP phenotype is associated with elevated markers of mucosal immune activation and low numbers of mucosal Treg, suggesting that factors other than immune activation account for this phenotype.
UR - http://www.scopus.com/inward/record.url?scp=84871881594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871881594&partnerID=8YFLogxK
U2 - 10.1089/aid.2012.0268
DO - 10.1089/aid.2012.0268
M3 - Article
VL - 29
SP - 172
EP - 177
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 1
ER -