Jgp. Wong et al., TCR-INDEPENDENT CD28-MEDIATED GENE-EXPRESSION IN PERIPHERAL-BLOOD LYMPHOCYTES FROM DONORS CHRONICALLY INFECTED WITH HIV-1, Immunology, 90(2), 1997, pp. 281-285
Complete activation of peripheral blood T cells requires both T-cell r
eceptor (TCR) stimulation and CD28 costimulation. Signalling pathways
associated specifically with CD28 are not well understood, however, be
cause ligation of CD28 in the absence of TCR stimulation does not give
rise to cellular responses in normal cells. In peripheral blood lymph
ocytes (PBL) from donors chronically infected with human immunodeficie
ncy virus-1 (HIV-1), CD28 can induce viral replication through an alte
rnative pathway that does not require TCR ligation. We have exploited
this observation to study CD28-mediated signal transduction using reve
rse transcriptase-mediated polymerase chain reaction (RT-PCR) to ampli
fy viral RNA. Independent ligation of CD28 on donor PBL induced expres
sion of the HIV-1 tat gene but not the interleukin-2 (IL-2) gene. Vira
l induction did not occur following pretreatment of cells with actinom
ycin D, suggesting it was mediated through transcriptional activation
of the viral long terminal repeat (LTR). rat was induced in the presen
ce of the protein kinase C inhibitor H-7, but was inhibited by cyclosp
orin A. Our results demonstrate that CD28 is linked directly to specif
ic signalling pathways leading to de novo induction of genes in PBL.