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How unusual cells may hold key to HIV control

Dec. 4, 2008
Courtesy Cell Press
and World Science staff

Rare peo­ple who man­age to con­trol HIV on their own are of­fer­ing sci­en­tists new ideas on how to sti­mu­late the im­mune sys­tem to kill vi­rus-in­fected cells. A new study iden­ti­fies spe­cif­ic qual­i­ties of the im­mune cells that suc­cess­fully de­stroy in­fected cells and may drive strate­gies for de­vel­op­ing new HIV vac­cines and ther­a­pies.

The rare in­di­vid­u­als dubbed “long-term non­pro­gres­sors” are able to con­tain HIV, the vi­rus be­hind AIDS, for many years with­out treat­ment.

Ev­i­dence sug­gests cer­tain vi­rus-spe­cif­ic im­mune cells, called CD8+ T cells, con­fer this abil­ity by de­stroying vi­rus-in­fected cell­s—but how re­mains un­known, said sen­ior study au­thor Mark Con­nors of the Na­tional In­sti­tute of Al­ler­gy and In­fec­tious Dis­ease in Be­thes­da, Md.

Us­ing new tools that pre­cisely meas­ure these cells’ kill­ing ca­pacity, Con­nors and col­leagues com­pared how cells from pro­gres­sors non-pro­gres­sors bat­tle the vi­rus. The CD8+ T cells of non-pro­gres­sors clob­bered in­fected cells by suc­cess­fully dis­pens­ing pro­tein mol­e­cules on­to them which poked holes in their pro­tec­tive mem­branes, the re­search­ers found. The im­mune cells sub­se­quently de­liv­ered a deadly mol­e­cule called granzyme B to the com­pro­mised cells.

Typical CD8+ T cells ac­com­plished this pro­cess poor­ly, in­ves­ti­ga­tors found. But these di­min­ished abil­i­ties were re­vers­i­ble af­ter treat­ment with cer­tain com­pounds, in­clud­ing phor­bol es­ter and cal­ci­um ionophore, sug­gest­ing pos­si­ble ther­a­peu­tic strate­gies, they added. The find­ings could be an “im­por­tant mile­stone for HIV vac­cine re­search,” said Ste­phen Migue­les, lead au­thor of the stu­dy, pub­lished in the Dec. 4 is­sue of the re­search jour­nal Im­mun­ity.

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Rare people who manage to control HIV on their own are offering new insights into how the immune system eliminates virus-infected cells, researchers say. A study identifies specific qualities of the immune cells that successfully destroy infected cells and may drive strategies for developing new HIV vaccines and therapies. The rare individuals dubbed “long-term nonprogressors” are able to contain HIV, the virus behind AIDS, for many years without treatment. Evidence suggests certain virus-specific immune cells, called CD8+ T cells, confer this ability by destroying virus-infected cells—but how remains unknown, said senior study author Mark Connors of the National Institute of Allergy and Infectious Disease in Bethesda, Md. Using new tools that precisely measure these cells’ killing capacity, Connors and colleagues compared how cells from progressors non-progressors battle the virus. The CD8+ T cells of nonprogressors clobbered infected cells by successfully dispensing protein molecules onto them which poked holes in their protective membranes, the researchers found. The immune cells subsequently delivered a deadly molecule called granzyme B to the compromised cells. The CD8+ T cells of progressors accomplished this process poorly, investigators found. But these diminished abilities were reversible after treatment with certain compounds, including phorbol ester and calcium ionophore, suggesting possible therapeutic strategies, they added. The findings could also “be an extremely important milestone for HIV vaccine research,” said Stephen Migueles, lead author of the study, published in the Dec. 4 issue of the research journal Immunity.