Im Rückblick womöglich interessant sind die frühen Diskussionen über die Balance der Immunzellen und deren Einfluss auf den Verlauf einer HIV-Infektion bzw. AIDS-Erkrankung. Daher erlaube ich mir, erneut einen meiner englischsprachigen Artikel zu dokumentieren, der am 10. Juni 1993 in der Kongress-Zeitung zur 9. Internationalen Aids-Konferenz in Berlin stand:

Long-term survival for all HIV-infected people is a distinct possibility, Dr. Jay Levy said yesterday. The head of the Cancer Research Institute at UC San Francisco also gave his reasoning on what path to take toward a goal that may seem far-fetched to many.

The most important clues come from studying people that have been living with the virus for a long time without developing AIDS or even signs of infection. Some long-term survivors have been carrying the virus for more than 15 years now; a few still have normal CD4+ cell counts. Up to 30 percent of these crucial T-cells may be harboring viral RNA, but in asymptomatic carriers, only one out of 400 CD4+ cells is actually producing virus. „It is important to determine the suppressive mechanism preventing the emergence of virulent, highly pathogenic virus strains,“ Levy said.

Recent observations in animal models throw some light on the role of relatively non-cytopathic strains that infect macrophages. According to Levy’s scenario, these cells are more than just unimportant bystanders. They might induce CD4+ cell death not by direct killing but indirectly through changes in the pattern of cytokines that are produced by infected macrophages. The cytokines, it is believed, could then lead to programmed cell death and loss of CD4+ cells.

Only after the stage is set by this mechanism, the fast replicating cytopathic strain emerges and starts killing off large numbers of CD4+ cells on a grand scale, leading to clear disease. „A long asymptomatic period then would depend on the ability of the host’s immune system to control even the replication of the non-cytopathic strains,“ Levy concluded.

By this rationale, another type of T-cell, a subset of CD8+ lymphocytes, might be turned into an ally for AIDS-prevention. Several laboratories have proved these cells suppress virus replication in CD4+ cells and macrophages without killing them. Further evidence for this theory stems from the fact that this particular type of CD8+ cells has been found in some children born to HIV-infected mothers but who themselves are not infected by the virus. Studying a pair of twins, one infected, the other not, Dr. Subhash Hira (University of Zambia) found that the CD8+ cells from both children showed anti-HIV activity. „An early strong cell-mediated anti-HIV response may have prevented the infection before antibody production,“ says Levy.

Focusing on the cellular response of the immune system, Levy explained that it could be activated by one subset of CD4+ cells and turned off by another. The boosters of the cellular response, termed TH1 cells, do their job by sending out cellular growth factors such as interleukin and gamma-interferon. TH2 cells, on the other hand, direct the production of antibodies that are of little or no benefit for HIV-infected individuals.

„We predict that the TH2 response suppresses CD8+ activity, leading to disease,“ Levy said, marking this subset of helper cells (CD4+, TH2) as the bad guys. The switch to disease progression is thrown when the TH2 response gets the upper hand over TH1. Levy’s lab has demonstrated that, in long-term survivors, as few as one CD8+ cell added to 20 infected CD4+ cells can control virus replication, whereas in AIDS patients large numbers of CD8+ cells are needed to control virus production by one CD4+ cell.

If confirmed, the sum of these observations might lead to new therapeutic approaches. Anything that can maintain the TH1 response of CD4+ cells or the anti-HIV activity of CD8+ cells „should keep the virus in check and prevent its emergence into a destructive strain,“ said Levy.