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

Joseph J. Mattapallil, Zeljka McBride, Peter Dailey, Satya Dandekar

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model, we performed a longitudinal study to determine the effect of antiretroviral therapy on the phenotype and functional potential of CD4+ T cells repopulating intestinal mucosa in human immunodeficiency virus infection. Severe depletion of CD4+ and CD4+ CD8+ T cells occurred in the intestinal mucosa during primary SIV infection. The majority of these cells were of activated memory phenotype. Phosphonate 9-[2- (phosphomethoxypropyl]adenine (PMPA) treatment led to a moderate suppression of intestinal vital loads and repopulation of intestinal mucosa by predominantly activated memory CD4+ T-helper cells. This repopulation was independent of the level of viral suppression. 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 cells was not observed in either jejunum or colon lamina propria. The majority of CD4+ T cells repopulating the intestinal mucosa following PMPA therapy were CD29(hi) and CD11a(hi). A subset of repopulating intestinal CD4+ T cells expressed Ki-67 antigen, indicating that local proliferation may play a role in the repopulation process. Although the majority of repopulating CD4+ T cells in the intestinal mucosa were functionally capable of providing B- and T-cell help, as evidenced by their expression of CD28, these CD4+ 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 of repopulating CD4+ T cells to produce IL-2. Hence, successful antiretroviral therapy should aim at complete suppression of viral loads in mucosal lymphoid tissues, such as intestinal mucosa.

Original languageEnglish (US)
Pages (from-to)6661-6669
Number of pages9
JournalJournal of Virology
Volume73
Issue number8
StatePublished - 1999

ASJC Scopus subject areas

  • Immunology

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