0000000000054802
AUTHOR
Georg Varga
Keratinocytes Determine Th1 Immunity during Early Experimental Leishmaniasis
Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation. Resistance to Leishmania (L.) major depends on the development of a L. major specific Th1 response, while Th2 differentiation results in susceptibility. There is growing evidence that the microenvironment of the early affected tissue delivers the initial triggers for Th-cell differentiation. To analyze this we studied differential gene expression in infected skin of resistant and susceptible mice 16h after parasite inoculation. Employing microarray technology, bioinformatics, laser-microdissection and in-situ-hybridization we found that the epidermis was the major source of immunomodulatory mediat…
β2Integrin 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 h…
LFA-1 Contributes to Signal I of T-Cell Activation and to the Production of Th1 Cytokines
The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the pro…