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β2 Integrin deficiency yields unconventional double-negative T cells distinct from mature classical natural killer T cells in mice.
- Source :
- Immunology; Oct2009, Vol. 128 Issue 2, p271-286, 16p, 7 Graphs
- Publication Year :
- 2009
-
Abstract
- Expressed on leucocytes, β<subscript>2</subscript> integrins (CD11/CD18) are specifically involved in leucocyte function. Using a CD18-deficient (CD18<superscript>−/−</superscript>) mouse model, we here report on their physiological role in lymphocyte differentiation and trafficking. CD18<superscript>−/−</superscript> mice present with a defect in the distribution of lymphocytes with highly reduced numbers of naïve B and T lymphocytes in inguinal and axillary lymph nodes. In contrast, cervical lymph nodes were fourfold enlarged harbouring unconventional T-cell receptor-αβ (TCR-αβ) and TCR-γδ CD3<superscript>+</superscript> CD4<superscript>−</superscript> CD8<superscript>−</superscript> (double-negative; DN) T cells that expanded in situ. Using adoptive transfer experiments, we found that these cells did not home to peripheral lymph nodes of CD18<superscript>wt</superscript> recipients but, like antigen-experienced T or natural killer (NK) T cells, recirculated through non-lymphoid organs. Lacking regulatory functions in vitro, CD18<superscript>−/−</superscript> TCR-αβ DN T cells did not suppress the proliferation of polyclonally activated CD4<superscript>+</superscript> or CD8<superscript>+</superscript> (single-positive; SP) T cells. Most interestingly, CD18<superscript>−/−</superscript> TCR-αβ DN T cells showed intermediate TCR expression levels, an absent activation through allogeneic major histocompatibility complex and a strong proliferative dependence on interleukin-2, hence, closely resembling NKT cells. However, our data oppose former reports, clearly showing that, because of an absent reactivity with CD1d-αGalCer dimers, these cells are not mature classical NKT cells. Our data indicate that CD18<superscript>−/−</superscript> TCR-αβ DN T cells, like NKT and TCR-γδ T cells, share characteristics of both adaptive and innate immune cells, and may accumulate as a compensatory mechanism to the functional defect of adaptive immunity in CD18<superscript>−/−</superscript> mice. [ABSTRACT FROM AUTHOR]
- Subjects :
- GENE expression
LEUCOCYTES
T cells
KILLER cells
LABORATORY mice
Subjects
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 128
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 44076443
- Full Text :
- https://doi.org/10.1111/j.1365-2567.2009.03116.x