β₂ Integrin deficiency yields unconventional double-negative T cells distinct from mature classical natural killer T cells in mice
Expressed on leucocytes, β₂ integrins (CD11/CD18) are specifically involved in leucocyte function. Using a CD18-deficient (CD18⁻/⁻) mouse model, we here report on their physiological role in lymphocyte differentiation and trafficking. CD18⁻/⁻ mice present with a defect in the distribution of lymphoc...
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Published in | Immunology Vol. 128; no. 2; pp. 271 - 286 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Oxford, UK : Blackwell Publishing Ltd
01.10.2009
Blackwell Publishing Ltd Blackwell Science Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Expressed on leucocytes, β₂ integrins (CD11/CD18) are specifically involved in leucocyte function. Using a CD18-deficient (CD18⁻/⁻) mouse model, we here report on their physiological role in lymphocyte differentiation and trafficking. CD18⁻/⁻ 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⁺ CD4⁻ CD8⁻ (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 CD18wt recipients but, like antigen-experienced T or natural killer (NK) T cells, recirculated through non-lymphoid organs. Lacking regulatory functions in vitro, CD18⁻/⁻ TCR-αβ DN T cells did not suppress the proliferation of polyclonally activated CD4⁺ or CD8⁺ (single-positive; SP) T cells. Most interestingly, CD18⁻/⁻ 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⁻/⁻ 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⁻/⁻ mice. |
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Bibliography: | http://dx.doi.org/10.1111/j.1365-2567.2009.03116.x |
ISSN: | 0019-2805 1365-2567 |
DOI: | 10.1111/j.1365-2567.2009.03116.x |