T cells consist of two major groups: CD4-positive T helper cells (who help other immune cells in mounting an effective response) and CD8-positive killer T cells. HIV infects and destroys CD4-positive cells, leaving patients with a crippled immune system. Throughout the course of HIV disease, however, patients have high levels of HIV-specific killer T cells. Early after initial infection, these cells are able to effectively kill the virus and reduce viral load. On the other hand, during the later stage of disease killer T cells, while still present, seem no longer able to control the virus. In an article in the November 4 issue of the Journal of Clinical Investigation, Premlata Shankar and colleagues from the Center for Blood Research at Harvard Medical School suggest why this might be the case.
The researchers compared killer T cells from HIV infected asymptomic individuals with those from symptomatic AIDS patients. They examined the killer cells' ability to eliminate target cells infected with laboratory strains of HIV on one hand, and with autologous virus (isolated from the patient) on the other. What they found is that killer T cells from asymptomatic individuals can recognize and kill both types of target cells. In contrast, the killer T cells from symptomatic patients, while still able to recognize and eliminate the laboratory strain targets, no longer killed target cells that were infected with their own, autologous, virus. This is likely due to the virus' propensity to mutate and the in inability of the patient's weakened immune system to keep up with the changing virus.
These results demonstrate that the high number of HIV-specific killer T cells found in AIDS patients are remnants of what used to be an effective response early after infection but no longer recognize the mutated autologous virus. Moreover, these findings reveal that conventional assays to measure killer T cell responses in HIV patients--which focus on responses to laboratory strains--do not accurately reflect but overestimate the response to the patient's autologous virus.
CONTACT:
Premlata Shankar
Harvard Medical School
The Center for Blood Research
800 Huntington Avenue
Boston, MA 02115
USA
PHONE: 617-278-3476
FAX: 617-278-3403
E-mail: shankar@cbr.med.harvard.edu
Journal of Clinical Investigation