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Lamina propria lymphocytes produce interferon-gamma and develop suppressor activity in response to lactoglobulin
1Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Insights
Human lamina propria lymphocytes (LPLs) respond to food antigens like lactoglobulin by proliferating and producing IFN-gamma. Subsequently, these LPLs develop antigen-nonspecific suppressor activity, impacting immune responses.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Human lamina propria lymphocytes (LPLs) are crucial for intestinal immunity.
- Understanding LPL responses to food antigens is vital for diagnosing and treating food allergies and intolerances.
Purpose of the Study:
- To investigate the in vitro immune response of human LPLs to common food antigens.
- To elucidate the mechanisms of LPL activation, proliferation, and cytokine production.
- To explore the development of LPL suppressor activity following antigen exposure.
Main Methods:
- Isolation of LPLs from healthy individuals undergoing gastric bypass surgery.
- Assaying LPL proliferation using [3H]thymidine incorporation.
- Measuring cytokine production (IL-2, IL-10, TNF-alpha, IFN-gamma) via ELISA.
- Utilizing CTLA4/Fc chimera and monoclonal antibodies (MAbs) to investigate cell surface molecule involvement.
Main Results:
- LPLs proliferated in response to keyhole limpet hemocyanin, ovalbumin, lactoglobulin, and phytohemagglutinin (PHA), but not yeast.
- Lactoglobulin and PHA responses involved CD28+ LPLs and antigen-presenting cells via the CD2 pathway, confirmed by inhibition with CTLA4/Fc and specific MAbs (CD2, CD58, CD80, CD86).
- LPLs produced significant IFN-gamma (100 ng/ml) in response to lactoglobulin, dependent on CD80/CD86, CD40/CD40L, and IL-12.
- Antigen exposure (lactoglobulin, ovalbumin, PHA) induced antigen-nonspecific suppressor activity in LPLs.
Conclusions:
- Human LPLs exhibit a biphasic response to food antigens: initial proliferation and cytokine production, followed by the development of suppressor activity.
- IFN-gamma production is a key feature of the LPL response to lactoglobulin, mediated by specific cell surface interactions and cytokines.
- The development of LPL suppressor activity suggests a regulatory mechanism within the intestinal immune system to control inflammatory responses to food antigens.
Abstract:
This study examines the in vitro response of human lamina propria lymphocytes (LPLs) to food antigens. LPLs were obtained from jejunum of healthy individuals undergoing gastric bypass operations for morbid obesity. Proliferation was assayed by [3H]thymidine incorporation and cytokine production by ELISA. LPLs proliferated in response to keyhole limpet hemocyanin, ovalbumin, lactoglobulin, and phytohemagglutinin (PHA), but not to yeast. The responses to lactoglobulin and PHA were inhibited by the CTLA4/Fc chimera and by MAbs against CD2, CD58, CD80, and CD86, indicating stimulation of CD28+ LPLs with antigen-presenting cells through activation of the CD2 pathway. Besides producing IL-2, IL-10, and TNF-alpha, LPLs synthesized large amounts of IFN-gamma (100 ng/ml) with lactoglobulin, a process dependent upon CD80/CD86, CD40/CD40L, and IL-12. After a three-day culture with lactoglobulin, ovalbumin, or PHA, LPLs developed suppressor activity that reduced proliferation of naive LPLs to these same stimuli. In summary, LPLs first respond to lactoglobulin by proliferation and IFN-gamma production, then by development of antigen nonspecific suppression.