Lee B, Bailer R, Rucker J, Kostman J, Tsang M, Doms R, Montaner L; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 6th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 6th 1999 Chic Ill. 1999 Jan 31-Feb 4; 6th: 168 (abstract no. 538).

The Wistar Institute, Philadelphia, PA.

In this report we sought to determine if PBMCs from individuals who lack CCR5 could polarize equivalently to TH1 and TH2 subtypes, and to quantify the amount of the major HIV-1 coreceptors, CCR5 and CXCR4, on TH1 and TH2 cells. We found that PBMCs from individuals homozygous for either the wild-type CCR5 gene or the DELTA32 ccr5 allele polarized to TH1 and TH2 cells equivalently suggesting that there is no gross impairment of TH1 or TH2 responses associated with the homozygous DELTA32 ccr5 phenotype. The amount of CCR5 and CXCR4 on TH1 vs TH2 cells was quantified using a FACs assay based on standardized calibrative beads. We found that CCR5 was preferentially expressed on TH1 cells and there was at least 5-fold more CXCR4 on TH2 vs TH1 cells. In support of this, the CXCR4 ligand SDF-1 mediated a greater Ca(2+) flux in TH2 vs TH1 cells. In addition, a semi-quantitative PCR entry assay indicated that an R5 virus (BaL) entered TH1 cells more efficiently while an X4 virus (IIIB) entered TH2 cells more efficiently. We also examined the expression of CCR1, CCR2, CCR3, CCR6, CXCR2, CXCR3, and STRL33 on TH1 vs TH2 cells using FACS analysis with monoclonal antibodies. Of these chemokine receptors, only CXCR2 and CCR6 were expressed at significant levels on TH1 or TH2 cells with CCR6 being slightly polarized on TH2 cells. In summary, DELTA32 ccr5 homozygous individuals can generate TH1/TH2 cells normally. Also, the level of CCR5 and CXCR4 receptor polarization observed between TH1 and TH2 cells may have consequences for the ability of these cells to support viral entry and replication in the context of varied immune activation.

Publication Types:

• Meeting Abstracts

Keywords:

• CCR6 protein, human
• CXCR6 protein, human
• Chemokine CXCL12
• Chemokines, CXC
• HIV-1
• IP10-Mig receptor
• Receptors, CCR5
• Receptors, CXCR4
• Receptors, Chemokine
• Receptors, Cytokine
• Th1 Cells
• Th2 Cells

Other ID:

• 20711776

UI: 102195306

From Meeting Abstracts