Loss of mucosal CD4 lymphocytes is an early feature of HIV infection

Abstract

SUMMARYT cell subsets in the gut mucosa are disliiicl populations and their imbalance in HIV has specilic implications in infection. Alterations in T cell subsets in duodenal biopsies vvere investigated in 17 asymptomatic HIV patients, 24 AIDS patienis and 10 controls wilh non-ulcer dyspepsia. Immunohistochemislry and immunofluorescence using MoAbs to CD3, CD4, CDS, CD68, CD45RA, CD45RO and gp 120 were performed on frozen sections. In the lamina propria, there was a significant depletion of CD4'^ cells at all stages of HIV, bul the density of CDS lamina propria cells was increased. Iniraepithelial lymphocytes were decreased in AIDS patients. There was a signilieunl correlation between cellular density and mucosal CD3 ' lymphocytes, and between mucosal CD3' and CDS' lymphocytes. Allhotigh mucosal CD4,CD45RO* 'memory" cells were decreased, CD8,CD45RO^ 'memory cells were increased. MucosatCD4' lymphocyte depletion occurred early in HIV, and thus their role in mueosal proleciion against opportunistic infeetion should be revised. Mucosal CD8' lymphocytes initially increased, but decreased when CD4 blood counts were depicted, perhaps contributing to loss ofhost protection against infection. Intraepitheiial lymphocyte depletion may also eontHbute lo opportunisiic infeciion.

The HIV-1-Specific Protein Casp8p41 Induces Death of Infected Cells through Bax/Bak

“…In acute infection of rhesus macaques with simian immunodeficiency virus (SIV), within days of infection, a similarly dramatic depletion of gastrointestinal (GI) tract CD4 T cells was observed (61). Phenotypic assessments of which gut CD4 T cells are lost during HIV-1/SIV infection of individuals (5,21,33,39,45,50,51,54) confirmed the preferential depletion of CD4 T cells and indicated that the majority of such cells express CCR5 and are therefore permissive to infection (30,46). The suggestion that the majority of these cells, which are later depleted, are infected was confirmed by ISH for HIV-1 and SIV during the acute phase of disease (22,32,39,53) as well as by flow cytometric sorting of defined T cell subsets followed by quantitative PCR assays for viral DNA (4, 16).…”

HIV infection and the gastrointestinal immune system

“…[36][37][38][39][40][41][42][43] Several of these studies examined CD4/CD8 ratios in the duodenum and peripheral blood in order to compare CD4 T-cell depletion between these two anatomical sites; the results also suggested that the GI tract was preferentially depleted of CD4 T cells. However, in another study, CD4/CD8 ratios in rectal biopsies of HIV-infected individuals were shown to be similar to those in peripheral blood.…”

Chronic CD4+T-Cell Activation and Depletion in Human Immunodeficiency Virus Type 1 Infection: Type I Interferon-Mediated Disruption of T-Cell Dynamics

“…During acute infection by HIV-1, the process of CD4 ϩ T-cell depletion is initiated by unchecked viral replication that occurs before an adaptive immune response is mounted (9,19,21,45,51,59,71,77). Concomitant with development of a cytotoxic T-lymphocyte (CTL) response and the consequent reduction in viral replication, however, the CD4 count rebounds to a quasi-steady-state level that is below the baseline CD4 count of HIV-negative (HIV Ϫ ) individuals and that decreases on the time scale of years (19,59).…”