Function of alpha beta TCR+ intestinal intraepithelial lymphocytes: Th1- and Th2-type cytokine production by CD4+CD8-

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K Fujihashi1, M Yamamoto, J R McGhee

  • 1Department of Oral Biology, University of Alabama at Birmingham 35294.

International Immunology
|November 1, 1993
PubMed

Insights

Intestinal intraepithelial lymphocytes (IELs) include CD4+ T cells that support mucosal antibody responses. These cells produce various cytokines, indicating roles in both Th1 and Th2 immunity.

Area of Science:

  • Immunology
  • Gastroenterology

Background:

  • The immunobiological functions of intestinal intraepithelial lymphocytes (IELs) remain incompletely understood.
  • Intestinal IEL T cells are known to exhibit cytotoxicity, produce cytokines, and perform regulatory roles.

Purpose of the Study:

  • To investigate the helper functions of CD4+ alpha beta TCR+ IELs in the small intestine.
  • To characterize the cytokine profiles of CD4+CD8- and CD4+CD8+ (double positive, DP) intestinal IELs.
  • To assess the role of IELs in mucosal antibody responses by co-culturing with Peyer's patch B cells.

Main Methods:

  • Cytokine-specific ELISPOT assays to quantify cytokine production.
  • Reverse transcription-polymerase chain reaction (RT-PCR) to analyze cytokine gene expression.
  • Co-culture experiments with Peyer's patch B cells to evaluate B cell help and Ig synthesis.

Main Results:

  • Freshly isolated CD4+CD8- IEL T cells primarily secrete Th2-type cytokines (IL-5, IL-4, IL-6).
  • DP T cells produce IL-5 and IL-6, but not IL-4, and both subsets contain IFN-gamma secreting Th1-type cells.
  • Neither CD4+CD8- nor DP T cells synthesize IL-2 in freshly isolated state, but stimulation with anti-CD3 induces IL-2 production.
  • CD4+ IEL T cells, but not CD4- IEL T cells, support Ig synthesis, including IgA responses, when co-cultured with PP B cells.

Conclusions:

  • CD4+ IEL T cells possess helper functions, contributing to mucosal antibody responses, particularly IgA.
  • Intestinal IEL T cell subsets exhibit distinct cytokine profiles, with CD4+CD8- cells showing a stronger Th2 bias.
  • Further investigation into IEL T cell subsets is crucial for understanding gut immunity and developing targeted therapies.

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