CCR5 and CXCR4 expression correlated with X4 and R5 HIV-1 infection yet not sustained replication in Th1 and Th2 cells

Objective: To investigate the infectivity of T-helper (Th)l and Th2 cells ( derived from ccr5 wild-type and homozygous ccr5 Delta 32) to R5 and X4 HIV- 1. Design: It remains unclear whether infection of Th1 and Th2 CD4 cells by R5 and X4 viruses mirrors their co-receptor expression profile as no direct q uantitation of coreceptor levels and infection has been performed. in addit ion, it is unknown whether the lack of CCR5 expression affects the degree o f Th1/Th2 polarization. Methods: Surface expression of CCR5 and CXCR4 was determined by quantitativ e fluorescence activated cell sorter analysis on in vitro differentiated Th 1 and Th2 cells. R5 (Ba-L) and X4 (IIIB) HIV-1 isolates were used for infec tion studies and the efficiency of viral entry was determined by quantitati ve real time polymerase chain reaction detection of reverse transcribed pro viral DNA. Results: Cell surface density of CCR5 molecules was eight-fold higher in Th 1 versus Th2 subsets (P = 0.005) whereas CXCR4 surface density was four-fol d higher in Th2 versus Th1 subsets (P = 0.006). Preferential infection and entry of Th1 cells by R5 HIV-1 was not associated with preferential replica tion, as eventually the R5-virus replicated to a higher level in Th2 cells in spite of lower initial viral infection/entry. By contrast, Th2 cells pre ferentially supported X4-virus infection and replication. High beta chemoki ne secretion by Th1 cells was associated with a lower R5 replication rate. Conclusions: Th1 and Th2 cells differ in their infection efficiency for R5 and X4 HIV-1. ccr5 Delta 32-homozygous individuals: maintain the ability fo r Th1/Th2 polarization, i.e., the expression of CCR5 is not required for Th 1/Th2 polarization. (C) 2001 Lippincott Williams & Wilkins.