Activated memory CD4(+) T helper cells repopulate the intestine early following antiretroviral therapy of simian immunodeficiency virus-infected rhesus macaques but exhibit a decreased potential to produce interleukin-2

Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model , we performed a longitudinal study to determine the effect of antiretrovir al therapy on the phenotype and functional potential of CD4(+) T cells repo pulating intestinal mucosa in human immunodeficiency virus infection. Sever e depletion of CD4(+) and CD4(+) CD8(+) T cells occurred in the intestinal mucosa during primary SIV infection. The majority of these cells were of ac tivated memory phenotype. Phosphonate 9-[2-(phosphomethoxypropyl]adenine (P MPA) treatment led to a moderate suppression of intestinal viral loads and repopulation of intestinal mucosa by predominantly activated memory CD4(+) T-helper cells. This repopulation was independent of the level of viral sup pression. Compared to preinfection values, the frequency of naive CD4(+) T cells increased following PMPA therapy, suggesting that new CD4(+) T cells were repopulating the intestinal mucosa. Repopulation by CD4(+) CD8(+) T ce lls was not observed in either jejunum or colon lamina propria. The majorit y of CD4(+) T cells repopulating the intestinal mucosa following PMPA thera py were CD29(hi) and CD11a(hi). A subset of repopulating intestinal CD4(+) T cells expressed Ki-67 antigen, indicating that local proliferation may pl ay a role in the repopulation process. Although the majority of repopulatin g CD4(+) T cells in the intestinal mucosa were functionally capable of prov iding B- and T-cell help, as evidenced by their expression of CD28, these C D4(+) T cells were found to have a reduced capacity to produce interleukin- 2 (IL-2) compared to the potential of CD4(+) T cells prior to SIV infection . Persistent viral infection may play a role in suppressing the potential o f repopulating CD4(+) T cells to produce IL-2. Hence, successful antiretrov iral therapy should aim at complete suppression of viral loads in mucosal l ymphoid tissues, such as intestinal mucosa.