Human immunodeficiency virus type 1 induces persistent changes in mucosal and blood γδ T cells despite suppressive therapy

γδ T cells are primarily found in the gastrointestinal mucosa and play an important role in the first line of defense against viral, bacterial, and fungal pathogens. We sought to examine the impact of human immunodeficiency virus type 1 (HIV-1) infection on mucosal as well as peripheral blood γδ T-cell populations. Our results demonstrate that HIV-1 infection is associated with significant expansion of Vδ1 and contraction of Vδ2 cell populations in both the mucosa and peripheral blood. Such changes were observed during acute HIV-1 infection and persisted throughout the chronic phase, without apparent reversion after treatment with highly active antiretroviral therapy (HAART). Despite an increase in the expression of CCR9 and CD103 mucosal homing receptors on peripheral blood γδ T cells in infected individuals, mucosal and peripheral blood γδ T cells appeared to be distinct populations, as reflected by distinct CDR3 length polymorphisms and sequences in the two compartments. Although the underlying mechanism responsible for triggering the expansion of Vδ1 γδ T cells remains unknown, HIV-1 infection appears to have a dramatic impact on γδ T cells, which could have important implications for HIV-1 pathogenesis.