PHENOTYPICALLY DEFINED MEMORY CD4+ CELLS ARE NOT SELECTIVELY DECREASED IN CHRONIC HIV DISEASE

Simultaneous measurements of phenotypically defined memory CD4(+) cell s and in vitro proliferation to three recall antigens (Ags; tetanus to roid, influenza, and Candida albicans) were performed in 53 HIV-seropo sitive subjects and 39 HIV-seronegative controls. The results indicate that the low proliferative responses to recall Ags of those who were HIV infected could be partly, but not fully, explained by a decrease o f phenotypically defined memory CD4(+) cells. This is, to our knowledg e, the first report of experiments that simultaneously measured memory CD4(+) cell numbers and function and then examined whether the low re sponses observed in seropositive subjects could be explained by low nu mbers of phenotypically defined memory CD4(+) cells. A central finding of the study, which argues against prevailing dogma, was that within the CD4(+) lymphocyte population, the proportion of cells displaying t he memory phenotype was not selectively decreased in HIV-seropositive subjects as compared with the proportion of these cells in seronegativ e homosexual controls. An entirely new finding of the study was that A IDS patients, many of whom were unresponsive to all three recall Ags t ested, actually had a significant increase in the proportion of CD4(+) cells with the memory phenotype, and this fraction approached 100% in subjects with CD4(+) cell numbers that were near zero. A final observ ation of the study, possible because some patients were on zidovudine (ZDV), was that there was no evidence that ZDV treatment led to an inc reased proliferative response to recall Ags in vivo. An in vitro study also found no effect of ZDV, dideoxycytidine (ddC), or azido-dideoxyu ridine (AZU) on proliferative responses to recall Ags.