ABSTRACT
During
acute and early human immunodeficiency virus type 1 (HIV-1) infection
(AEI) more than 50% of CD4+ T cells are
preferentially depleted from the gastrointestinal (GI) lamina propria.
To better understand the underlying mechanisms, we studied virological
and immunological events within the peripheral blood (PB) and GI tract
during AEI. A total of 32 AEI subjects and 18 uninfected controls
underwent colonic biopsy. HIV-1 viral DNA and RNA levels were
quantified in CD4+ T cells derived from the GI tract
and PB by using real-time PCR. The phenotype of infected cells was
characterized by using combinations of immunohistochemistry and in situ
hybridization. Markers of immunological memory, activation, and
proliferation were examined by flow cytometry and immunohistochemistry,
and the host-derived cytotoxic cellular response was examined by using
immunohistochemistry. GI CD4+ T cells harbored, on
average, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1
RNA levels than PB CD4+ T cells during AEI. HIV-1
RNA was detected in both “activated” and“
nonactivated” mucosal CD4+ T cells.
A significantly higher number of activated and proliferating T cells
were detected in the GI tract compared to the PB, and a robust
cytotoxic response (HIV-1 specificity not determined) was detected in
the GI tract as early as 18 days postinfection. Mucosal
CD4+ T-cell depletion is multifactorial. Direct
viral infection likely accounts for the earliest loss of
CD4+ T cells. Subsequently, ongoing infection of
susceptible CD4+ T cells, along with
activation-induced cellular death and host cytotoxic cellular response,
are responsible for the persistence of the
lesion.
Repeated Immunization with Recombinant gp160 Human Immunodeficiency Virus (HIV) Envelope Protein in Early HIV‐1 Infection: Evaluation of the T Cell Proliferative Response