Prolonged dominance of clonally restricted CD4(+) T cells in macaques infected with simian immunodeficiency viruses

The repertoire of functional CD4(+) T lymphocytes in human immunodeficiency virus type 1-infected individuals remains poorly understood, To explore th is issue, we have examined the clonality of CD4(+) T cells in simian immuno deficiency virus (SIV)-infected macaques by assessing T-cell receptor compl ementarity-determining region 3 (CDR3) profiles and sequences, A dominance of CD4(+) T cells expressing particular CDR3 sequences was identified withi n certain V beta-expressing peripheral blood lymphocyte subpopulations in t he infected monkeys. Studies were then done to explore whether these domina nt CD4(+) T cells represented expanded antigen-specific cell subpopulations or residual cells remaining in the course of virus-induced CD4(+) T-cell d epletion, Sequence analysis revealed that these selected CDR3-bearing CD4() T-cell clones emerged soon after infection and dominated the CD4(+) T-cel l repertoire for up to 14 months. Moreover, inoculation of chronically infe cted macaques with autologous SIV-infected cell lines to transiently increa se plasma viral loads in the monkeys resulted in the dominance of these sel ected CDR3-bearing CD4(+) T cells. Both the temporal association of the det ection of these clonal cell populations with infection and the dominance of these cell populations following superinfection with SIV suggest that thes e cells may be SIV specific, Finally, the inoculation of staphylococcal ent erotoxin B superantigen into SIV-infected macaques uncovered a polyclonal b ackground underlying the few dominant CDR3-bearing CD4(+) T cells, demonstr ating that expandable polyclonal CD4(+) T-cell subpopulations persist in th ese animals. These results support the notions that a chronic AIDS virus in fection can induce clonal expansion, in addition to depletion of CD4(+) T c ells, and that some of these clones may be SIV specific.