Chemokine and cytokine mediated loss of regulatory T cells in lymph nodes during pathogenic simian immunodeficiency virus infection.
Regulatory T cells (T(reg)) play key roles in immune regulation through multiple modes of suppression. The effects of HIV-1 infection on T(reg) levels in lymphoid tissues remain incompletely understood. To explore this issue, we have measured the levels of forkhead box protein 3 (FOXP3)-positive cells and associated immunomodulatory genes in a pathogenic simian immunodeficiency virus/macaque model and found that a loss of T(reg) in lymph nodes occurred following simian immunodeficiency virus infection. Changes in expression of the ligands for CXCR3, CCR4, and CCR7 and the cytokines TGF-beta and IL-2 were all linked to this loss of T(reg), which in turn was linked with increased levels of cellular activation. Our findings identify three mechanisms that likely contribute to SIV-driven loss of T(reg), including reduced levels of cytokines associated with T(reg) differentiation and altered expression of agonist and antagonist chemokines. The loss of T(reg) and the associated cellular activation in lymphoid tissues is consistent with the events in HIV-1-infected individuals and suggest that components of the T(reg) differentiation and trafficking network could be targets for therapeutic intervention.
Qin
Shulin
S
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Sui
Yongjun
Y
Soloff
Adam C
AC
Junecko
Beth A Fallert
BA
Kirschner
Denise E
DE
Murphey-Corb
Michael A
MA
Watkins
Simon C
SC
Tarwater
Patrick M
PM
Pease
James E
JE
Barratt-Boyes
Simon M
SM
Reinhart
Todd A
TA
D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008252:Macaca fascicularis; D054398:Receptors, CCR4 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D008024:Ligands; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D016212:Transforming Growth Factor beta