Factors related to loss of HIV-specific cytotoxic T lymphocyte activity.
OBJECTIVE
To identify factors associated with loss of in vitro stimulated anti-HIV cytotoxic T lymphocyte (CTL) activity.


METHODS
Immunological, virological and other characteristics of individuals who sustained anti-HIV CTL activity for prolonged periods with viral replication suppressed below detectable levels were compared with those that lost anti-HIV CTL activity under the same circumstances. Forty-four individuals, all but one receiving highly active antiretroviral therapy or combination therapy, were followed for 56 months. Virus load, lymphocyte counts, CD28 expression on CD8 T cells, in vitro restimulated HIV-specific CTL and T cell proliferation were assessed at regular intervals.


RESULTS
Anti-HIV CTL responses were maintained throughout by 20 individuals with consistently detectable HIV replication and in 17 of 24 individuals with sustained suppression of HIV replication. As a group, the seven who lost anti-HIV CTL were older, had weaker baseline anti-HIV CTL activity, higher historical virus loads, lower historical and contemporary CD4 T cell counts and a lower percentage of CD8 T cells expressing CD28. Multivariate analysis suggested that CD4 T cell counts and anti-HIV CTL amplitude at study onset were independently associated with CTL loss in these individuals, as was percentage of CD8 T cells expressing CD28 at study's end. There was a significant direct correlation between nadir CD4 T cell counts and duration of anti-HIV CTL persistence after suppression of viral replication.


CONCLUSIONS
Most HIV-infected individuals retain CD8 anti-HIV CTL with in vitro proliferative potential, even when antigen is limited. Those who lose HIV-specific CTL responses generally show past or current evidence of severe disease progression or activity.
Gamberg
Jane
J
Immunology Program, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St John's, Newfoundland, Canada A1B 3V6.
Barrett
Lisa
L
Bowmer
M Ian
MI
Howley
Constance
C
Grant
Michael
M
D000328:Adult; D018106:CD28 Antigens / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D018655:Lymphocyte Count; D015999:Multivariate Analysis; D014779:Virus Replication / Q000276:immunology
D018106:CD28 Antigens