Beta(2) integrin deficiency yields unconventional double-negative T cells distinct from mature classical natural killer T cells in mice.
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.
Oreshkova
Tsvetelina
T
Department of Dermatology and Allergic Diseases, Ulm University, D-89081 Ulm, Germany.
Wang
Honglin
H
Seier
Anne M
AM
Sindrilaru
Anca
A
Varga
Georg
G
Grabbe
Stephan
S
Scharffetter-Kochanek
Karin
K
Peters
Thorsten
T
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018920:Coculture Techniques; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008206:Lymphatic Diseases / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018821:CD18 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta