Magnitude and complexity of rectal mucosa HIV-1-specific CD8+ T-cell responses during chronic infection reflect clinical status.
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.


RESULTS
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.


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.
Critchfield
J William
JW
Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, USA.
Young
Delandy H
DH
Hayes
Timothy L
TL
Braun
Jerome V
JV
Garcia
Juan C
JC
Pollard
Richard B
RB
Shacklett
Barbara L
BL
D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002908:Chronic Disease; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006304:Health Status; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D012007:Rectum / Q000276:immunology / Q000473:pathology; D019562:Viral Load
D044966:Anti-Retroviral Agents