Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Carol, Mónica; Lambrechts, A; Gossum, A. Van; Libin, Myriam; Goldman, Michel; Mascart‐Lemone, F.

doi:10.1136/gut.42.5.643

Cited by 92 publications

(65 citation statements)

References 24 publications

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“…A significant reduction in the total intestinal mucosa CD4+TL was observed in HIV+ patients, confirming previous studies (11,12,(30)(31)(32). This reduction did not correlate with disease stage, probably because of the small number of patients in group 2.…”

Section: Discussionsupporting

confidence: 76%

Immunopathology of the duodenal mucosa of HIV-positive patients during combined antiretroviral therapy

Machado

Pagliari

Caiafa

et al. 2006

Braz J Med Biol Res

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The objective of the present study was to evaluate the duodenal mucosa of HIV-infected patients during antiretroviral therapy. This was an observational study conducted on HIV-positive patients and a control group. Group 1 comprised 22 HIV-negative individuals while 38 HIV-positive individuals were classified according to the CDC 1993 classification into group 2 (A1 or A2) or group 3 (B2, A3, B3, C2, C3). All subjects were submitted to upper gastrointestinal endoscopy with duodenal biopsies. Qualitative, semi-quantitative and quantitative histological analyses were performed. Results were considered significant when P < 0.05. A higher prevalence of inflammatory infiltrate and eosinophilia was observed in the HIV group, together with a reduction in mucosal CD4+ lymphocyte (L) counts [median (lower-upper quartiles), 12.82 (8.30-20.33), 6.36 (1.75-11.66) and 1.75 (0.87-3.14) in groups 1, 2 and 3, respectively] which was not correlated with disease stage. The extent of CD4+L count reduction was similar in blood and duodenal mucosa. Normal CD8+L and CD45RO+L counts, and normal numbers of macrophages and antigen-presenting cells were also found in the HIV patients. The cytokine pattern did not differ among groups. Tissue HIV, assessed by p24 antigen, correlated with a higher CD45RO+L count (77.0 (61-79.8) and 43.6 (31.7-62.8) in p24+ and p24-, respectively, P = 0.003), and IL-4 positivity (100 and 48.2% in p24+ and p24-, respectively, P = 0.005). The duodenal mucosa of HIV+ patients showed a relatively preserved histological architecture. This finding may be characteristic of a population without opportunistic infections and treated with potent antiretroviral therapy, with a better preservation of the immune status.

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Section: Discussionsupporting

confidence: 76%

Immunopathology of the duodenal mucosa of HIV-positive patients during combined antiretroviral therapy

Machado

Pagliari

Caiafa

et al. 2006

Braz J Med Biol Res

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“…The human gut mucosa seems to be in a state of controlled inflammation under normal conditions, since intestinal intraepithelial and lamina propria lymphocytes spontaneously secrete IFN-␥ (13,19,26). We observed that IFN-␥ dramatically increases the expression of TLRs and potentiates the capacity of DCs to secrete cytokines, but only in response to E. coli and V. parvula.…”

Section: Discussionmentioning

confidence: 61%

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Karlsson¹,

Larsson²,

Wold

et al. 2004

Infect Immun

119

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The normal gastrointestinal bacterial flora is crucial for the maturation of acquired immunity via effects on antigen-presenting cells (APCs). Here we investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal microflora. Purified human monocytes and monocyte-derived DCs were stimulated with UV-inactivated gram-positive (Lactobacillus plantarum and Bifidobacterium adolescentis) and gram-negative (Escherichia coli and Veillonella parvula) bacterial strains. Monocytes produced higher levels of interleukin 12p70 (IL-12p70) and tumor necrosis factor (TNF), as detected by an enzyme-linked immunosorbent assay, in response to L. plantarum than in response to E. coli and V. parvula. In contrast, DCs secreted large amounts of IL-12p70, TNF, IL-6, and IL-10 in response to E. coli and V. parvula but were practically unresponsive to L. plantarum and B. adolescentis. The lack of a response to the gram-positive strains correlated with lower surface expression of Toll-like receptor 2 (TLR2) on DCs than on monocytes. The surface expression of TLR4 on DCs was undetectable when it was analyzed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that TLR4 is expressed at a low density on DCs. Gamma interferon increased the expression of TLR4 on DCs and also potentiated the cytokine response to the gram-negative strains. Our results indicate that when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, and they become unresponsive to probiotic gram-positive bacteria. These results may have important implications for the abilities of different groups of commensal bacteria to regulate mucosal and systemic immunity.

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“…However, in normal LPL in humans, the in vitro response is dominated by IFN-␥ (28). Indeed, in previous studies from both us and others, the spontaneous production of cytokines by freshly isolated lamina propria T cells is dominated by IFN-␥ (29,30), and in our previous study of freshly isolated PP T cells, we also found an excess of IFN-␥-secreting cells (14).…”

Section: Discussionmentioning

confidence: 89%

Human Peyer’s Patch T Cells Are Sensitized to Dietary Antigen and Display a Th Cell Type 1 Cytokine Profile

Nagata

McKenzie

Pender

et al. 2000

The Journal of Immunology

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Animal studies have demonstrated that feeding Ags induces regulatory (Th2, Th3) cells in Peyer’s patches (PP), which migrate to the periphery and produce immunomodulatory cytokines such as IL-4, IL-10, or TGF-β. In this work we have attempted to extend this paradigm to man by analyzing the response of human PP T cells to in vitro challenge with the common dietary Ag β-lactoglobulin (βlg) of cow’s milk. PP T cells stimulated with βlg showed enhanced proliferation compared with blood T cells from the same patient. Increased expression of CD25 and the Th1-associated chemokine receptor CCR5 was also seen on CD4+ and CD8+ PP T cells, but not blood T cells, stimulated with βlg. By enzyme-linked immunospot assay and RT-PCR, the PP T cell recall response to βlg and casein was dominated by IFN-γ, with negligible IL-4, IL-5, IL-10, or TGF-β. To help explain the PP T cell response to βlg, we examined IL-12 expression. Both IL-12p40 and -p35 transcripts were abundantly expressed in PP, but not in adjacent normal ileal mucosa. Immunoreactive IL-12p40-containing cells were present below the PP dome epithelium. Furthermore, in culture, PP, but not paired PBMC, spontaneously released IL-12p70. These results suggest that the human response to oral Ags in the gut may be different from that in rodents.

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Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Abstract: (Gut 1998;42:643-649)

Cited by 92 publications

References 24 publications

Immunopathology of the duodenal mucosa of HIV-positive patients during combined antiretroviral therapy

Immunopathology of the duodenal mucosa of HIV-positive patients during combined antiretroviral therapy

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Human Peyer’s Patch T Cells Are Sensitized to Dietary Antigen and Display a Th Cell Type 1 Cytokine Profile

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