PERIPHERAL EXPANSION OF PREEXISTING MATURE T-CELLS IS AN IMPORTANT MEANS OF CD4(-CELL REGENERATION HIV-INFECTED ADULTS() T)

The CD4(+) T-cell pool in HIV-infected patients is in a constant state of flux as CD4(+) T cells are infected and destroyed by HIV and new c ells take their place. To study T-cell survival, we adoptively transfe rred peripheral blood lymphocytes transduced with the neomycin phospho transferase gene between syngeneic twin pairs discordant for HIV infec tion. A stable fraction of marked CD4(+) T cells persisted in the circ ulation for four to eighteen weeks after transfer in all patients. Aft er this time there was a precipitous decline in marked cells in three of the patients. At approximately six months, marked cells were in lym phoid tissues in proportions comparable to those found in peripheral b lood. In two patients, the proportion of total signal for the transgen e (found by PCR analysis) in the CD4/CD45RA(+) T-cell population relat ive to the CD4/CD45RO(+) population increased in the weeks after cell infusion. These findings indicate that genetically-marked CD4(+) T cel ls persist in vivo for weeks to months and that the CD4+ T-cell pool i n adults is maintained mostly by the division of mature T cells rather than by differentiation of prethymic stem cells. Thus, after elements of the T-cell repertoire are lost through HIV infection, they may be difficult to replace.