Toll-like receptor and chemokine receptor expression in HIV-infected T lymphocyte subsets.
In the present investigation, flow cytometric techniques were utilized to evaluate 100 cases of HIV and 20 normal controls for CXCR4, CCR5, and TLR4 expression in CD4-positive T cells, CD8-positive T cells, regulatory T cells, and Th17 cells, and fluorescence intensity values were determined. TLR4 was expressed by CD4+ T cells and CD8+ T cells in 97 cases, by regulatory T cells in 88 of 95 cases, and by Th17 cells in 93 of 95 cases, while it remained negative in all 20 normal controls. These data indicate that TLR4 upregulation is not limited to gram-negative bacterial infection nor is expression limited to myeloid cells. Upregulation of TLR4 in HIV patients may either be directly or indirectly related to the presence of the virus. CXCR4 was positively expressed by CD4+ T cells in 96 HIV cases, CD8+ T cells in 95, regulatory T cells in 89 of 95 cases evaluated, and Th17 cells in all 92 cases evaluated, while expression remained negative in the majority of normal controls. CCR5 was positively expressed by CD4+ and CD8+ T cells in all 100 HIV cases and by regulatory T cells in 89 of 95 cases evaluated, while expression was negative in most CD4+ and regulatory T cells of normal controls. Statistically significant differences were detected when TLR4 expression by CD4+ and CD8+ T cells was compared to stage of disease. TLR4 expression decreased as infection progressed from acute phase to AIDS. In addition, expression of TLR4 by all T cell subsets was slightly decreased in patients receiving HAART therapy. Results also reveal a positive correlation between CXCR4, CCR5, and TLR4 expression indicating that TLR4 expression and chemokine expression pathways are linked.
Miller Sanders
Catherine
C
University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216, USA. csanders@hudsonalpha.com
Cruse
Julius M
JM
Lewis
Robert E
RE
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002648:Child; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism* / Q000821:virology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
D019380:Anti-HIV Agents; C527276:CXCR4 protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4