Important note: Information in this article was accurate in March 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, March 1, 1999
Daniel J. DeNoon, Senior Editor
Taking advantage of this early defect in lymphoid cytotoxic lymphocytes (CTLs), new findings suggest, HIV establishes the permanent vantage point from which it disseminates throughout the body and destroys the rest of the immune system.
"This defect in cytolytic molecules in lymphoid tissues during primary HIV infection might be relevant to the lack of control of HIV dissemination," suggested Jan Andersson of the QUEST study group, Stockholm, Sweden.
Andersson reported the findings in a late-breaker session of the 6th Conference on Retroviruses and Opportunistic Infections, held January 31-February 4, 1999, in Chicago, Illinois.
The international QUEST team is studying the effects of highly active antiretroviral therapy (HAART) when given during primary HIV infection. Prior to receiving HAART, study subjects undergo extensive immunologic and virologic studies.
Andersson's group studied immune responses in lymphoid tissues. Previous studies have focused on more easily attainable samples of peripheral blood.
The scenario they uncovered is complex. Soon after infection, HIV sets off a terrific immune activation. On days 1 to 5 after infection, there is a huge increase in (beta) chemokine release, and there is excessive interferon gamma production. No increase is seen in interleukin 10 (IL-10), but there is a significant increase in IL- 12. The T-helper type 1 (Th1) cytokine IL-2 and the Th2 cytokine IL-4 are produced in greater quantities - paradoxically, by the same cells. Thus a great number of antiviral cytokines are produced during a time when virus production also increases.
"These results provide evidence for strong but aberrant immune activation in primary HIV infection," Andersson suggested. "The dichotomy between cytokine excess and the inability to control HIV dissemination is a unique feature of HIV-1 infection."
During all this confusion, another perhaps crucial defect occurs. In lymphoid tissues there was a terrific upregulation of granzyme A production by CTL. Granzyme A is the carrier molecule for perforin, which kills cells attacked by CTL.
"Much to our surprise, we found a significant increase in granzyme A - 28 times normal - but not in perforin," Andersson said. "That may be of tremendous importance in the elimination of infected cells during primary infection."
Exactly how HIV performs this complex task of confusing and disarming the immune system remains to be discovered. This answer promises to be of immense value to the development of HIV vaccines. And the Andersson findings show that even in its earliest stages, HIV is a unique pathogen.
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