Dynamics of CCR5 expression by CD4(+) T cells in lymphoid tissues during simian immunodeficiency virus infection.
Early viral replication and profound CD4(+) T-cell depletion occur preferentially in intestinal tissues of macaques infected with simian immunodeficiency virus (SIV). Here we show that a much higher percentage of CD4(+) T cells in the intestine express CCR5 compared with those found in the peripheral blood, spleen, or lymph nodes. In addition, the selectivity and extent of the CD4(+) T-cell loss in SIV infection may depend upon these cells coexpressing CCR5 and having a "memory" phenotype (CD45RA(-)). Following intravenous infection with SIVmac251, memory CD4(+) CCR5(+) T cells were selectively eliminated within 14 days in all major lymphoid tissues (intestine, spleen, and lymph nodes). However, the effect on CD4(+) T-cell numbers was most profound in the intestine, where cells of this phenotype predominate. The CD4(+) T cells that remain after 14 days of infection lacked CCR5 and/or were naive (CD45RA(+)). Furthermore, when animals in the terminal stages of SIV infection (with AIDS) were examined, virtually no CCR5-expressing CD4(+) T cells were found in lymphoid tissues, and all of the remaining CD4(+) T cells were naive and coexpressed CXCR4. These findings suggest that chemokine receptor usage determines which cells are targeted for SIV infection and elimination in vivo.
Veazey
R S
RS
Division of Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA. veazey@tpc.tulane.edu
Mansfield
K G
KG
Tham
I C
IC
Carville
A C
AC
Shvetz
D E
DE
Forand
A E
AE
Lackner
A A
AA
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008221:Lymphoid Tissue / Q000737:chemistry*; D008253:Macaca mulatta; D019713:Receptors, CCR5 / Q000032:analysis*; D019718:Receptors, CXCR4 / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*
D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D017493:Leukocyte Common Antigens