Beta(2) Integrin Deficiency Yields Unconventional Double-negative T Cells Distinct from Mature Classical Natural Killer T Cells in Mice

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2009 Sep 11

PMID 19740384

Citations 6

Authors

Tsvetelina Oreshkova

Honglin Wang

Anne M Seier

Anca Sindrilaru

Georg Varga

Stephan Grabbe

Karin Scharffetter-Kochanek

Thorsten Peters

Affiliations

Soon will be listed here.

Abstract

Expressed on leucocytes, beta(2) 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-alphabeta (TCR-alphabeta) and TCR-gammadelta 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 CD18(wt) recipients but, like antigen-experienced T or natural killer (NK) T cells, recirculated through non-lymphoid organs. Lacking regulatory functions in vitro, CD18(-/-) TCR-alphabeta DN T cells did not suppress the proliferation of polyclonally activated CD4(+) or CD8(+) (single-positive; SP) T cells. Most interestingly, CD18(-/-) TCR-alphabeta 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-alphaGalCer dimers, these cells are not mature classical NKT cells. Our data indicate that CD18(-/-) TCR-alphabeta DN T cells, like NKT and TCR-gammadelta 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.

Citing Articles

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