Decreased levels of recent thymic emigrants in peripheral blood of simian immunodeficiency virus-infected macaques correlate with alterations within the thymus.
The thymus is responsible for de novo production of CD4(+) and CD8(+) T cells and therefore is essential for T-cell renewal. The goal of this study was to assess the impact of simian immunodeficiency virus (SIV) infection on the production of T cells by the thymus. Levels of recent thymic emigrants within the peripheral blood were assessed through quantification of macaque T-cell receptor excision circles (TREC). Comparison of SIV-infected macaques (n = 15) to uninfected macaques (n = 23) revealed stable or increased TREC levels at 20 to 34 weeks postinfection. Further assessment of SIV-infected macaques (n = 4) determined that TREC levels decreased between 24 and 48 weeks postinfection. Through the assessment of longitudinal time points in three additional SIVmac239-infected macaques, the SIV infection was divided into two distinct phases. During phase 1 (16 to 30 weeks), TREC levels remained stable or increased within both the CD4 and CD8 T-cell populations. During phase 2 (after 16 to 30 weeks), TREC levels declined in both T-cell populations. As has been described for human immunodeficiency virus (HIV)-infected patients, this decline in TREC levels did at times correlate with an increased level of T-cell proliferation (Ki67(+) cells). However, not all TREC decreases could be attributed to increased T-cell proliferation. Further evidence for thymic dysfunction was observed directly in a SIVmac239-infected macaque that succumbed to simian AIDS at 65 weeks postinfection. The thymus of this macaque contained an increased number of memory/effector CD8(+) T cells and an increased level of apoptotic cells. In summary, reduced levels of TREC can be observed beginning at 16 to 30 weeks post-SIV infection and correlate with changes indicative of dysfunction within the thymic tissue. SIV infection of macaques will be a useful model system to elucidate the mechanisms responsible for the thymic dysfunction observed in HIV-infected patients.
Sodora
Donald L
DL
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113, USA. Donald.Sodora@UTSouthwestern.edu
Milush
Jeffrey M
JM
Ware
Felecia
F
Wozniakowski
Aneta
A
Montgomery
Lisa
L
McClure
Harold M
HM
Lackner
Andrew A
AA
Marthas
Marta
M
Hirsch
Vanessa
V
Johnson
R Paul
RP
Douek
Daniel C
DC
Koup
Richard A
RA
D000818:Animals; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D002465:Cell Movement; D015329:Gene Rearrangement, T-Lymphocyte; D020287:In Situ Nick-End Labeling; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000473:pathology* / Q000503:physiopathology