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Pollen-induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis.

Desai MB, Gavrilova T, Liu J, Patel SA, Kartan S, Greco SJ, Capitle E, Rameshwar P - Clin Transl Immunology (2013)

Bottom Line: In cases with reduced inflammation, MSCs could become immune-enhancer cells.The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests.This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

View Article: PubMed Central - PubMed

Affiliation: New Jersey Medical School, Rutgers University , Newark, NJ, USA.

ABSTRACT
Mesenchymal stem cells (MSCs) are promising cellular suppressor of inflammation. This function of MSCs is partly due to their licensing by inflammatory mediators. In cases with reduced inflammation, MSCs could become immune-enhancer cells. MSCs can suppress the inflammatory response of antigen-challenged lymphocytes from allergic asthma. Although allergic rhinitis (AR) is also an inflammatory response, it is unclear if MSCs can exert similar suppression. This study investigated the immune effects (suppressor vs enhancer) of MSCs on allergen-stimulated lymphocytes from AR subjects (grass or weed allergy). In contrast to subjects with allergic asthma, MSCs caused a significant (P<0.05) increase in the proliferation of antigen-challenged lymphocytes from AR subjects. The increase in lymphocyte proliferation was caused by the MSCs presenting the allergens to CD4(+) T cells (antigen-presenting cells (APCs)). This correlated with increased production of inflammatory cytokines from T cells, and increased expressions of major histocompatibility complex (MHC)-II and CD86 on MSCs. The specificity of APC function was demonstrated in APC assay using MSCs that were knocked down for the master regulator of MHC-II transcription, CIITA. The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests. Thus, we deduced that the contrasting immune effects of MSCs for antigen-challenged lymphocytes on AR and allergic asthma could be disease specific. It is possible that the enhanced inflammation from asthma might be required to license the MSCs to become suppressor cells. This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

No MeSH data available.


Related in: MedlinePlus

Cytokine production and expressions of MHC-II and CD86 in mesenchymal stem cells (MSCs). (a) Antigen-presenting cell (APC) assays were established with activated peripheral blood mononuclear cells (PBMCs) and pulsed or unpulsed MSCs. The cells were obtained from three subjects with allergic rhinitis (AR) and ragweed sensitivity (Table 1: S8, S13, S22). After 48 h, the media were analyzed in duplicate with cytokine protein arrays. The densities of the background cytokines (PBMCs alone) were subtracted from the experimental points and then presented as fold change of pulsed MSCs/unpulsed MSCs, ±s.d., n=6. (b) Pulsed and unpulsed MSCs from the APC assays were studied for MHC-II and CD86 by flow cytometry using donors S17, S19, and S22 (Table 1). The analyses were done on CD105+/CD3−/CD25−. *P<0.05 vs other cytokines.
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fig5: Cytokine production and expressions of MHC-II and CD86 in mesenchymal stem cells (MSCs). (a) Antigen-presenting cell (APC) assays were established with activated peripheral blood mononuclear cells (PBMCs) and pulsed or unpulsed MSCs. The cells were obtained from three subjects with allergic rhinitis (AR) and ragweed sensitivity (Table 1: S8, S13, S22). After 48 h, the media were analyzed in duplicate with cytokine protein arrays. The densities of the background cytokines (PBMCs alone) were subtracted from the experimental points and then presented as fold change of pulsed MSCs/unpulsed MSCs, ±s.d., n=6. (b) Pulsed and unpulsed MSCs from the APC assays were studied for MHC-II and CD86 by flow cytometry using donors S17, S19, and S22 (Table 1). The analyses were done on CD105+/CD3−/CD25−. *P<0.05 vs other cytokines.

Mentions: The media were analyzed with cytokine protein arrays in duplicate. The baseline cytokine production was subtracted from the test samples and the resulting densities were normalized to the internal controls. The results were then presented as fold changes of pulsed MSCs/unpulsed MSCs. The results indicated >1.5-fold increases for all cytokines. Particularly, there were significant increases in IL-2, IL-6, and IL-7. IFN-γ was increased slightly above the 1.5-fold level (Figure 5a).


Pollen-induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis.

Desai MB, Gavrilova T, Liu J, Patel SA, Kartan S, Greco SJ, Capitle E, Rameshwar P - Clin Transl Immunology (2013)

Cytokine production and expressions of MHC-II and CD86 in mesenchymal stem cells (MSCs). (a) Antigen-presenting cell (APC) assays were established with activated peripheral blood mononuclear cells (PBMCs) and pulsed or unpulsed MSCs. The cells were obtained from three subjects with allergic rhinitis (AR) and ragweed sensitivity (Table 1: S8, S13, S22). After 48 h, the media were analyzed in duplicate with cytokine protein arrays. The densities of the background cytokines (PBMCs alone) were subtracted from the experimental points and then presented as fold change of pulsed MSCs/unpulsed MSCs, ±s.d., n=6. (b) Pulsed and unpulsed MSCs from the APC assays were studied for MHC-II and CD86 by flow cytometry using donors S17, S19, and S22 (Table 1). The analyses were done on CD105+/CD3−/CD25−. *P<0.05 vs other cytokines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232057&req=5

fig5: Cytokine production and expressions of MHC-II and CD86 in mesenchymal stem cells (MSCs). (a) Antigen-presenting cell (APC) assays were established with activated peripheral blood mononuclear cells (PBMCs) and pulsed or unpulsed MSCs. The cells were obtained from three subjects with allergic rhinitis (AR) and ragweed sensitivity (Table 1: S8, S13, S22). After 48 h, the media were analyzed in duplicate with cytokine protein arrays. The densities of the background cytokines (PBMCs alone) were subtracted from the experimental points and then presented as fold change of pulsed MSCs/unpulsed MSCs, ±s.d., n=6. (b) Pulsed and unpulsed MSCs from the APC assays were studied for MHC-II and CD86 by flow cytometry using donors S17, S19, and S22 (Table 1). The analyses were done on CD105+/CD3−/CD25−. *P<0.05 vs other cytokines.
Mentions: The media were analyzed with cytokine protein arrays in duplicate. The baseline cytokine production was subtracted from the test samples and the resulting densities were normalized to the internal controls. The results were then presented as fold changes of pulsed MSCs/unpulsed MSCs. The results indicated >1.5-fold increases for all cytokines. Particularly, there were significant increases in IL-2, IL-6, and IL-7. IFN-γ was increased slightly above the 1.5-fold level (Figure 5a).

Bottom Line: In cases with reduced inflammation, MSCs could become immune-enhancer cells.The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests.This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

View Article: PubMed Central - PubMed

Affiliation: New Jersey Medical School, Rutgers University , Newark, NJ, USA.

ABSTRACT
Mesenchymal stem cells (MSCs) are promising cellular suppressor of inflammation. This function of MSCs is partly due to their licensing by inflammatory mediators. In cases with reduced inflammation, MSCs could become immune-enhancer cells. MSCs can suppress the inflammatory response of antigen-challenged lymphocytes from allergic asthma. Although allergic rhinitis (AR) is also an inflammatory response, it is unclear if MSCs can exert similar suppression. This study investigated the immune effects (suppressor vs enhancer) of MSCs on allergen-stimulated lymphocytes from AR subjects (grass or weed allergy). In contrast to subjects with allergic asthma, MSCs caused a significant (P<0.05) increase in the proliferation of antigen-challenged lymphocytes from AR subjects. The increase in lymphocyte proliferation was caused by the MSCs presenting the allergens to CD4(+) T cells (antigen-presenting cells (APCs)). This correlated with increased production of inflammatory cytokines from T cells, and increased expressions of major histocompatibility complex (MHC)-II and CD86 on MSCs. The specificity of APC function was demonstrated in APC assay using MSCs that were knocked down for the master regulator of MHC-II transcription, CIITA. The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests. Thus, we deduced that the contrasting immune effects of MSCs for antigen-challenged lymphocytes on AR and allergic asthma could be disease specific. It is possible that the enhanced inflammation from asthma might be required to license the MSCs to become suppressor cells. This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

No MeSH data available.


Related in: MedlinePlus