WESTPORT, Sep 01 (Reuters Health) - Antigenic stimulation of primary CD4 T cells up-regulates both CCR5, the receptor for R5-tropic HIV, and CXCR4, the receptor for X4-tropic HIV, according to a report in the September 1st issue of Blood.

R5-tropic, or nonsyncytium-inducing, viruses favor macrophage targets, whereas X4-tropic, or syncytium-inducing, viruses favor T lymphocytes, the authors explain. CCR5 is expressed mainly on effector/memory T cells and seems to be more important in HIV transmission, while CXCR4 is mainly expressed on naive CD4+ T cells.

In an effort to address the effects of propagation of HIV after T-cell stimulation, Dr. Andreas Meyerhans, of the Institute of Medical Microbiology and Hygiene, in Homburg, Germany, and colleagues studied the kinetics of CCR5 and CXCR4 surface expression and HIV replication in CD4 T cells stimulated by antigen-presenting cells.

Prior to stimulation, T cells expressed CXCR4, but CCR5 was barely detectable, the authors report. After stimulation, however, CCR5 and CXCR4 expression was up-regulated in comparable amounts. CCR5 and CXCR4 expression was maximal 3 days after antigen-specific CD4 T-cell stimulation, the report indicates.

Antigen-specific CD4 T-cell stimulation significantly promoted the productive HIV infection with both R5- and X-4 tropic viruses, the investigators note, with peak HIV-p24 antigen levels within 7 days after infection.

Exogenous IL-2 prolonged the HIV proliferative response but had no influence on the kinetics of CCR5 and CXCR4 up-regulation, the results indicate.

"The stimulation of primary CD4 T cells leads to a significant up-regulation of CCR5 and CXCR4 and an HIV-permissive phenotype of the cells," the authors conclude. "This provides evidence that antigenic stimulation per se cannot be the reason for the preference of R5-tropic viruses in HIV transmission."

"Overall, the results strengthen the important role of antigen for efficient HIV replication," the researchers assert. "As bacterial superantigens are very common antigens, these antigens might contribute significantly to the HIV load in vivo."

(From ReutersHealth)