Increased expression of interferon-gamma in hyperplastic lymph nodes from HIV-infected patients

Abstract

SUMMARY Polyclonal B cell activation is characteristic of HIV infection and occurs in the presence of severe CD4+ lymphocyte depletion. In contrast, CD4+ lymphocytes are the dominant T cell in the reactive lymphoid tissues of patients not infected with HIV. In this study, lymph node biopsies from eight HIV‐infectcd patients with persistent generalized lymphadenopathy syndrome (PGL) were assessed for IL‐lβ, IL‐2, IL‐4, IL‐6, IL‐10, interferon‐gamma (IFN‐γ) and tumour necrosis factor‐beta (TNF‐β) gene expression using the polymerase chain reaction (PCR). The cytokine gene expression of two cases of reactive adenopathy in patients not infected with HIV was assessed for comparison. IFN‐γ was expressed much more strongly in the PGL samples than in control reactive lymphoid tissues, whereas the other cytokines were expressed to a similar extent in both types of tissues. IFN‐γ may have an important role in maintaining the adenopalhy of HIV‐infected patients. Expression of cytokines such as IL‐2, IL‐4 and IL‐10 in HIV nodes may be adequate to allow the recruitment of naive B cells to the reactive process.

Increased soluble CD14 serum levels and altered CD14 expression of peripheral blood monocytes in HIV-infected patients

“…T lymphocytes from HIV-infected patients express [37,38] and secrete [39] IFN--, at an increased rate, but are unable to produce iL-4 [39]. In this regard it is of interest thai both cyiokines modulating CD14 derive from different subsets of T helper cells, IFN-7 from Thl and IL-4 from Th2 cells.…”

“…Expression of membrane-bound CDi4 and release of soluble CD14 by monocytes is down-regulated by T cellderived IL-4 and interferon-gamma (IFN-7) [35,36]. T lymphocytes from HIV-infected patients express [37,38] and secrete [39] IFN--, at an increased rate, but are unable to produce iL-4 [39]. In this regard it is of interest thai both cyiokines modulating CD14 derive from different subsets of T helper cells, IFN-7 from Thl and IL-4 from Th2 cells.…”

Increased levels of interferon-gamma (IFN-γ), IL-4 and transforming growth factor-beta (TGF-β) mRNA expressing blood mononuclear cells in human HIV infection

“…Such patients were also shown to have high levels of HIV antigenreactive Th I -like cells which, upon recognition of HIV recombinant antigens, responded by secretion of IFN-y (Lolli et al, manuscript submitted). IFN-y was also found in brain autopsy specimens [12] and over-expressed in lymph nodes from HIVinfected patients [13]. Elevated serum levels ofTGF-)?…”

Expansion or Depletion of T Follicular Helper Cells During HIV Infection: Consequences for B cell Responses

“…Tfh cells have been shown to express high levels of IL-6R that correlated with increased IL-6 levels during chronic SIV infection 61 . Recent studies have implicated IFNγ as a potential mechanism for the accumulation of Tfh in the GC 71 and Boyle et al 72 showed that IFN γ levels were significantly enhanced in the LN of HIV infected patients. Expansion of Tfh cells have been reported in a number of autoimmune diseases such as SLE 73 , Sjogren’s syndrome 74 , Rheumatoid Arthritis 75 and Juvenile Dermatomyositis 20 .…”