Selective depletion of rectal lamina propria rather than lymphoid aggregate CD4 lymphocytes in HIV infection

Abstract

SUMMARYThe goal of this study was to examine the changes in lymphocyte populations in rectal mucosa during HIV infection and to study their relationship to mucosal immunity and to systemic depletion of CD4 lymphocytes. Rectal biopsies from 58 HIV-infected subjects and eight controls were studied. Frozen rectal tissue sections were stained with antibodies to CD4, CD3, CD8, and markers for macrophages. HIV-infected subjects were divided into early stage (no opportunistic infections) and AIDS groups. There was profound depletion of rectal lamina propria CD4 lymphocytes (16% and 6% of normal content in early and AIDS groups, respectively). However, lymphoid aggregate CD4 lymphocytes were far less severely depleted (69% and 40% of normal content, respectively). The extent of lymphoid aggregate CD4 lymphocyte depletion generally parallelled the CD4 lymphocyte depletion in the blood. CD8 lymphocyte content in both the lamina propria and lymphoid aggregates usually were increased, particularly in early-stage patients. Macrophage contents were usually normal in the HIV-infected groups. We conclude that rectal lamina propria and lymphoid aggregates are distinct compartments differing markedly in their CD4 lymphocyte content during HIV infection. In light of this and an increased number of apoptotic cells which were noted in rectal lamina propria in HIV-infected subjects, we hypothesize that intestinal lamina propria could be a site of rapid CD4 lymphocyte destruction during HIV infection.

HIV infection and the gastrointestinal immune system

“…26 Later studies, also using immunohistochemistry, confirmed that that the GI tract was indeed significantly depleted of CD4 T cells. 27,31,32 Moreover, these observations were made in both the large and small intestine, indicating that the depletion of GI CD4 T cells involves the entire bowel. However, these studies were somewhat restricted in that the majority of the HIV-infected individuals studied were chronically infected with HIV or in the late stage of AIDS.…”

Mucosal Plasma Cell Repertoire During HIV-1 Infection

“…Impaired GC formation, structure, and function in the systemic compartment are well described in HIV-1-infected patients (59, 65, 66) and may also relate to changes in the isotype distribution of mucosal B cells during HIV-1 infection. Prominent data from HIV-1-infected humans and SIV-infected macaques suggest that widespread depletion of CD4 ϩ T cells in the effector lamina propria occurs early after infection, while these cells remain more numerous in mucosal inductive sites (12,39,67). Although these GC T cells could supply the signaling that B cells require to initiate CSR (see below), several studies have also shown that these cells can harbor HIV-1 or SIV (36,39,68).…”

“…Underlying these high rates may be the impaired Ab responses to luminal Ags, which complicate HIV-1 infection (5-10). The mechanisms of this impairment of B cell function may derive from T cell (11,12) or intrinsic B cell defects (13)(14)(15)(16). HIV-1 has been proposed to induce intrinsic defects in B cells through selective depletion of cells expressing Ig H chains of the third variable region family (V H 3) (17)(18)(19)(20)(21), which comprise about half of the expressed circulating V H repertoire (22)(23)(24)(25)(26).…”

Do most lymphocytes in humans really reside in the gut?

“…Recent studies have highlighted the importance of early depletion of CD4 + T cells in the gut occurring after infection of humans with HIV-1 [1][2][3][4][5][6] and rhesus macaques with SIV [7][8][9][10][11]. These authors have observed a rapid and large reduction in the fraction of CD4 + T cells in the lamina propria (LP) of the gut, and several follow-up papers argued that this ''first cut'' is important for disease progression [12][13][14][15][16].…”