Conserved T-cell receptor repertoire in simian immunodeficiency virus-infected rhesus monkeys.
Studies to assess the possibility that the HIV may encode a superantigen that plays a role in the depletion of functional CD4+ lymphocytes in the infected individual have yielded discrepant results. The problem in performing conclusive examinations of this issue may be attributed, at least in part, to the difficulty of prospectively studying individuals from before their infection until the time of profound CD4+ lymphocyte loss. To determine whether the AIDS virus deletes particular subpopulations of V beta-expressing lymphocytes, we have employed an animal model of AIDS, the simian immunodeficiency virus (SIV)-infected macaque monkey. Rhesus monkeys were experimentally infected with SIVmac and studied prospectively. A PCR-based quantitative method for assessing TCR repertoire was employed to analyze the expression of 24 V beta and 30 V alpha gene families in the monkeys. Although circulating PBL were increased in number by 3 wk after SIVmac infection, the expanded lymphocyte populations exhibited no significant perturbation in their TCR V beta repertoires. PBL obtained from monkeys before and 0.5 to 3 years after infection displayed no significant change in V beta and V alpha gene family expression. Finally, no deletion of V beta-expressing cell subpopulations could be demonstrated in purified CD4+ lymphocytes from infected monkeys. This was true even for monkeys whose blood contained less than 200 CD4+ lymphocytes/microliters. These results indicate that the TCR repertoire is conserved in SIVmac-infected rhesus monkeys and suggests that mechanisms other than superantigen-induced deletion must be responsible for CD4+ lymphocyte loss in these animals.
Chen
Z W
ZW
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772.
Kou
Z C
ZC
Shen
L
L
Reimann
K A
KA
Letvin
N L
NL
D000818:Animals; D001483:Base Sequence; D015870:Gene Expression; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta