AIDSWEEKLY Plus, 12 Aug 1996
Daniel J. DeNoon, Senior Editor

Exhaustive immunological studies of Zambian women who remain uninfected despite repeated sexual exposure to HIV revealed only one difference from matched, unexposed women.

"The high risk seronegative women had significantly lower proliferative responses to an alloreactive stimulator cell line," said John F. Krowka of the University of California, San Francisco.

Krowka announced the study findings - and offered several possible explanations for them - at the XI International Conference on AIDS, held July 7-12, 1996 in Vancouver, British Columbia, Canada.

Krowka and colleagues obtained blood samples from 18 HIV negative women married to HIV infected men (the high-risk group) and compared them to blood samples from HIV negative women married to HIV negative men (the low-risk group).

The two groups of women were matched for age, number of children, pregnancy, and duration of marriage.

The blood samples were assayed for peripheral blood lymphocytes (PBL) proliferative responses to Candida, alloantigens, or phytohemagglutinin (PHA); CD4(+) and CD8(+) T-lymphocyte levels; interleukin 2 (IL-2) production by PBL in response to HIV envelope peptides; plasma levels of the C-C cytokines RANTES, MIP1(alpha), and MIP1(beta); and CD8(+) suppressor-phenotype T lymphocytes.

"Of all the parameters tested only the proliferative responses of PBL to one particular allogeneic stimulator cell line (IBC21) were significantly different between high-risk and low-risk women," Krowka et al. wrote in their presentation abstract. "In three independent experiments, the responses to ... IBC21 were significantly lower in PBL from high-risk women."

The researchers offered several interpretations of their data:

• Genetic differences may have predisposed the immune systems of the high-risk women to resist HIV infection.
• Previous exposure to alloantigens may have protected the high-risk women against HIV.
• Exposure to sub-infectious doses of HIV and/or exposure to types of HIV that cross-react with alloantigens may have helped the high-risk women resist infection.
• The selectively lower proliferative responses to alloantigen seen in the high-risk women may have been due to sequestration of T cells that cross-react with HIV and IBC21. These T cells may be sequestered in the lymph nodes, mucosa, or other locations distinct from the peripheral blood.

Krowka et al. are currently investigating these hypotheses.

Interestingly, no protective effects were seen for high levels of C-C cytokines. These cell-produced antiviral substances were recently reported to have anti-HIV activity, but their role in the pathogenesis of HIV disease has been hotly debated.

"Our data is not showing a protective effect for these cytokines," Krowka said.

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