NAIVE T CELLS ARE RECONSTITUTED IN PATIENTS FOLLOWING THERAPY WITH PROTEASE INHIBITORS

FEBRUARY 1998

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CHICAGO -- The immune systems of HIV-positive patients receiving potent therapy with protease inhibitors are able to replenish their supply of "naive" CD4+ T cells in addition to their supply of CD4+ "memory" cells, even when the naive cells have been eliminated, according to a study conducted by Emory University and Centers for Disease Control and Prevention (CDC) researchers. Results of the research were presented at the 5th Conference on Retroviruses and Opportunistic Infections in Chicago February 1-5.

The CD4+ T cell population includes "memory" cells, which have been exposed to a specific antigen and are able to recognize and react to that antigen if it presents again, and "naive" cells, which have not yet been exposed to an antigen but are available for future activation. Progressive HIV-1 infection is characterized by the depletion and later by the absence of naive CD4+ T cells. The lack of these naive cells may leave HIV-positive patients unable to respond to new infections.

Earlier research has led investigators to believe that once naive T cells are completely depleted, they are not able to be reconstituted and that any increases in naive T cell populations following protease inhibitor therapy apply only to T cells that were present before therapy began.

In the recent Emory/CDC study, however, Emory investigator Richard L. Hengel, M.D., and his colleagues were able to corroborate earlier work (Autran, et.al., 1997) showing that naive T cell populations begin to replenish themselves following the institution of protease inhibitor therapy, both in patients who already had measurable populations of naive T cells when therapy began and in patients with no measurable naive T cells.

In addition, the Emory and CDC researchers plotted the kinetics of the T cell reconstitution over time, showing that naive cells begin to reconstitute almost immediately in patients with these cells already present at baseline, and continue to rise over a period of months at a rate exceeding memory cells. In the group of patients with no naive cells present at baseline, half began to reconstitute naive cells after several months of protease inhibitor therapy, but the rate of accumulation of memory cells exceeded that of naive cells in this group.

Research still needs to be conducted on just how effective these reconstituted naive cells are in fighting opportunistic infections, Dr. Hengel points out, and on the likely origins of these cells.

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