Naïve CD4 T cells inhibit CD28-costimulated R5 HIV replication in memory CD4 T cells

AUTOR(ES)

Mengozzi, Manuela

FONTE

The National Academy of Sciences

RESUMO

Stimulation with antibodies to CD3 and CD28 coimmobilized on beads can be used to significantly expand T cells ex vivo. With CD4 T cells from HIV-infected patients, this expansion usually is accompanied by complete suppression of viral replication, presumed to be caused by down-regulation of the viral coreceptor CCR5 and up-regulation of CCR5 ligands. Here we show that this suppression occurs in total CD4 T cells acutely infected with R5 HIV, but not in purified CD62L− memory CD4 T cells. The lack of complete suppression in these memory cells, typically comprising 10–40% of total CD4 T cells, occurs despite high levels of CCR5 ligand secretion and down-regulation of CCR5. Significantly, adding back naïve or CD62L+ memory CD4 T cells inhibits the viral replication in the CD62L− cells, with the naïve cells capable of completely repressing the virus. Although this inhibition was previously thought to be specific to bead-bound anti-CD3/CD28 stimulation, we show that the same suppression is obtained with sufficiently strong anti-CD3/B7.1 stimulation. Our results show that inhibitory mechanisms, expressed predominantly by strongly stimulated naïve CD4 T cells and mediated independently of CCR5-binding chemokines, play a role in the inhibition of R5 HIV replication in CD4 T cells upon CD28 costimulation.

Documentos Relacionados

• HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28.
• CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly
• Differential transcription directed by discrete gamma interferon promoter elements in naive and memory (effector) CD4 T cells and CD8 T cells.
• Naïve and Memory CD4 T Cells Differ in Their Susceptibilities to Human Immunodeficiency Virus Type 1 Infection following CD28 Costimulation: Implications for Transmission and Pathogenesis
• Spontaneous proliferation, a response of naïve CD4 T cells determined by the diversity of the memory cell repertoire