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Do the CD45RO+CD8+ intestinal intraepithelial T lymphocytes have the characteristics of memory cells?
1Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903.
Insights
Human intraepithelial lymphocytes (IEL) share cytotoxic T lymphocyte (CTL) activity with memory cells. However, IEL CD8+ T cells cannot be perpetuated long-term, unlike CD4+ T cells which show non-specific cytotoxicity.
Area of Science:
- Immunology
- Gastrointestinal immunology
Background:
- Human intraepithelial lymphocytes (IEL) are primarily CD45RO+ memory CD8+ T cells residing in the gut.
- The characteristics of IEL compared to circulating memory T cells are not fully understood.
Purpose of the Study:
- To investigate whether IEL share other characteristics with circulating CD45RO+ memory lymphocytes.
- To determine the cytotoxic T lymphocyte (CTL) potential and long-term culture capacity of IEL and lamina propria lymphocytes (LPL).
Main Methods:
- Comparison of IEL size and adhesion molecule expression with peripheral blood (PB) T cells.
- Assessment of allo-CTL activity in IEL and LPL after varying culture periods with alloantigen and cytokines (IL-2, IL-4, IL-6).
- Long-term propagation of alloantigen-stimulated IEL, LPL, and PB CD8+ T cell lines to assess phenotype and function.
Main Results:
- IEL do not exhibit increased adhesion molecule density compared to PB T cells, though CD54 and CD58 expression is higher.
- Both IEL and LPL develop allo-CTL activity after 2.5 weeks of culture with alloantigen and IL-2.
- Long-term culture of mucosal lymphocytes results in a predominant CD4+ T cell subset displaying potent, non-specific cytotoxicity, while CD8+ T cells do not persist.
Conclusions:
- IEL share allo-CTL activity with circulating memory cells, but differ in adhesion molecule expression and size.
- Mucosal CD8+ T cells cannot be maintained long-term under these culture conditions.
- Mucosal CD4+ T cell lines exhibit significant non-specific cytotoxic activity, a characteristic distinct from circulating memory T cells.
Abstract:
Human intraepithelial lymphocytes (IEL) are predominantly CD45RO+ (memory) CD8+ T lymphocytes located between intestinal epithelial cells. This study determines whether IEL share other characteristics with circulating CD45RO+ lymphocytes. Memory cells are large and have an upregulated expression of adhesion molecules. In contrast, the majority of IEL are the same size as peripheral blood (PB) T cells. In addition, IEL do not have an increased density of adhesion molecules, although a larger percentage express CD54 and CD58 compared to PBL. Allo-CTL activity, demonstrated by CD45RO+ PBL, could not be shown using either IEL or lamina propria lymphocytes (LPL) after a 5-day culture with alloantigen. However, after a 2.5-week culture with allogeneic PBL and interleukin-2 (IL-2), both IEL and LPL were capable of this cytotoxic function. The addition of IL-4 or IL-6 did not alter CTL activity by mucosal lymphocytes. Alloantigen-stimulated IEL, LPL, and PB CD8+ T cell lines were propagated for up to 16 weeks. All lines demonstrated alloantigen-specific proliferation. The PB CD8+ T lymphocytes maintained their phenotype and allo-CTL activity. In contrast, the CD4+ subset in the IEL and LPL became the predominant lymphocyte type and demonstrated potent lytic activity that was not alloantigen specific. This study shows that (1) IEL do not have increased density of adhesion molecules, (2) mucosal lymphocytes demonstrate allo-CTL activity, (3) CD8+ T cells in the mucosa cannot be perpetuated long-term by alloantigen and IL-2, and (4) mucosal CD4+ T cell lines demonstrate marked alloantigen-nonspecific cytotoxicity. The only characteristic shared by IEL and circulating memory cells is allo-CTL activity.