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Magnitude and complexity of rectal mucosa HIV-1-specific CD8+ T-cell responses during chronic infection reflect clinical status.
- Source :
-
PloS one [PLoS One] 2008; Vol. 3 (10), pp. e3577. Date of Electronic Publication: 2008 Oct 30. - Publication Year :
- 2008
-
Abstract
- Background: The intestinal mucosa displays robust virus replication and pronounced CD4+ T-cell loss during acute human immunodeficiency virus type 1 (HIV-1) infection. The ability of HIV-specific CD8+ T-cells to modulate disease course has prompted intensive study, yet the significance of virus-specific CD8+ T-cells in mucosal sites remains unclear.<br />Methods and Findings: We evaluated five distinct effector functions of HIVgag-specific CD8+ T-cells in rectal mucosa and blood, individually and in combination, in relationship to clinical status and antiretroviral therapy (ART). In subjects not on ART, the percentage of rectal Gag-specific CD8+ T-cells capable of 3, 4 or 5 simultaneous effector functions was significantly related to blood CD4 count and inversely related to plasma viral load (PVL) (p<0.05). Polyfunctional rectal CD8+ T-cells expressed higher levels of MIP-1beta and CD107a on a per cell basis than mono- or bifunctional cells. The production of TNFalpha, IFN-gamma, and CD107a by Gag-specific rectal CD8+ T-cells each correlated inversely (p<0.05) with PVL, and MIP-1beta expression revealed a similar trend. CD107a and IFN-gamma production were positively related to blood CD4 count (p<0.05), with MIP-1beta showing a similar trend. IL-2 production by rectal CD8+ T-cells was highly variable and generally low, and showed no relationship to viral load or blood CD4 count.<br />Conclusions: The polyfunctionality of rectal Gag-specific CD8+ T-cells appears to be related to blood CD4 count and inversely related to PVL. The extent to which these associations reflect causality remains to be determined; nevertheless, our data suggest a potentially important role for mucosal T-cells in limiting virus replication during chronic infection.
- Subjects :
- Anti-Retroviral Agents therapeutic use
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes drug effects
Chronic Disease
Cohort Studies
Disease Progression
Female
HIV Infections blood
HIV Infections drug therapy
HIV Seropositivity blood
HIV Seropositivity immunology
Health Status
Humans
Immunity, Mucosal drug effects
Intestinal Mucosa drug effects
Intestinal Mucosa immunology
Lymphocyte Count
Male
Rectum immunology
Rectum pathology
Viral Load
CD8-Positive T-Lymphocytes immunology
HIV Infections immunology
HIV Infections pathology
HIV-1 immunology
Immunity, Mucosal immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 3
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 18974782
- Full Text :
- https://doi.org/10.1371/journal.pone.0003577