By Steve Mitchell

WESTPORT, Sep 01 (Reuters Health) - Patients infected with human herpesvirus 8 (HHV-8) develop CD8+ cytotoxic T lymphocytes specific for HHV-8 that may play a role in controlling the virus and consequently Kaposi's sarcoma (KS), researchers report in the September issue of The Journal of Infectious Diseases.

"We now have experimental proof that CD8 T cells specific for HHV-8 develop during HHV-8 infection, and that these cells are likely to be central to the control of HHV-8 replication and thus, the development of KS," Dr. Charles R. Rinaldo, of the University of Pittsburgh, in Pennsylvania, told Reuters Health.

The findings suggest that treatments for KS "will need to boost anti-HHV-8 T-cell immunity in order to control HHV-8 infection," Dr. Rinaldo said. "We suspect that highly active antiretroviral therapy (HAART) is doing this by driving down HIV-1 load, thereby boosting host immunity including recovery of T-cell responses to HHV-8."

Dr. Rinaldo and colleagues characterized the cytotoxic T-lymphocyte response to five HHV-8 homologues of lytic proteins in 14 individuals seropositive for HHV-8. The researchers detected HLA class I-restricted CD8+ CTL responses to one or more of the HHV-8 lytic proteins in all subjects whether they were infected with HIV-1 or not. In contrast, none of the five HHV-8 seronegative controls tested positive for the HHV-8-specific CD8+ cells.

The seven subjects infected with both HHV-8 and HIV-1 exhibited greater anti-CTL reactivity to glycoprotein H than did the seven infected only with HHV-8. The subjects infected with both viruses also exhibited a strong, inverse correlation between HIV-1 load and glycoprotein H-specific CTL lysis.

The findings may have implications for transplant patients infected with HHV-8. "It is likely that anti-HHV-8 T-cell immunity is the critical, operative immune function controlling the herpesvirus in these patients as well," Dr. Rinaldo said, "and that their immunity to this virus and to KS is depressed by their immunosuppressive drug therapy."

"Thus," he added, "treatment regimens that affect anti-HHV-8 T-cell responses, either positively or negatively, will alter HHV-8 associated diseases." In support of this idea, he noted that "reduction of immunosuppressive drug therapy results in 'spontaneous' remission of KS in such patients."

"Although KS is no longer as significant in the US due to HAART, it is still a significant problem in Third World countries, including non-HIV-1-related KS in Africa," Dr. Rinaldo said. "Our and other such studies are the beginning of the understanding of anti-HHV-8 immunity that is needed for development of an HHV-8 vaccine."

Dr. Rinaldo's team is currently conducting further studies to define the role of CD8 T-cell responses to HHV-8 in relation to development of KS, he said.

(From ReutersHealth)