Biomedical subjects

Heike Unsoeld

Publications and source records attributed to Heike Unsoeld.

4 recordsLinked to original sources

PubMed2006

CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion.

The role of type I IFN signaling in CD8 T cells was analyzed in an adoptive transfer model using P14 TCR transgenic CD8 T cells specific for lymphocytic choriomeningitis virus (LCMV) but deficient in type I IFNR. In the present study, we demonstrate severe impairment in the capacity of P14 T cells lacking type I IFNR to expand in normal type I IFNR wild-type C57BL/6 hosts after LCMV infection. In contrast, following infection of recipient mice with recombinant vaccinia virus expressing LCMV glycoprotein, P14 T cell expansion was considerably less dependent on type I IFNR expression. Lack of type I IFNR expression by P14 T cells did not affect cell division after LCMV infection but interfered with clonal expansion. Thus, direct type I IFN signaling is essential for CD8 T cell survival in certain viral infections.

Adoptive Transfer↗

PubMed2005

Complex memory T-cell phenotypes revealed by coexpression of CD62L and CCR7.

Antigen-experienced T cells have been divided into CD62L+ CCR7+ central memory (TCM) and CD62L- CCR7- effector memory (TEM) cells. Here, we examined coexpression of CD62L and CCR7 in lymphocytic choriomeningitis virus-specific memory CD8 T cells from both lymphoid and nonlymphoid tissues. Three main points emerged: firstly, memory cells frequently expressed a mixed CD62L- CCR7+ phenotype that differed from the phenotypes of classical TEM and TCM cells; secondly, TCM cells were not restricted to lymphoid organs but were also present in significant numbers in nonlymphoid tissues; and thirdly, a major shift from a TCM to TEM phenotype was found in memory cells that had been stimulated repetitively with antigen.

Animals↗

PubMed2004

Constitutive expression of CCR7 directs effector CD8 T cells into the splenic white pulp and impairs functional activity.

Antigenic stimulation down-regulates CCR7 on effector T cells. To analyze the importance of CCR7 down-regulation, transgenic (tg) mice constitutively expressing CCR7 were generated. CD8 T cells with defined Ag specificity were obtained by breeding CCR7-tg mice with P14 TCR-tg mice specific for lymphocytic choriomeningitis virus. Transgenic CCR7 expression did not impair proliferation of P14.CCR7 T cells induced by lymphocytic choriomeningitis virus infection, but prevented CCR7 down-regulation. Compared with wild-type P14 effector cells, P14.CCR7 effector cells, expressing the CCR7 transgene, were increased in the spleen, but decreased in blood and peripheral tissues. Moreover, P14.CCR7 effector cells localized almost exclusively in the splenic white pulp, whereas P14 effector cells were excluded from splenic white pulp cords and were found preferentially in the red pulp. Functional experiments further revealed that P14.CCR7 effector cells were impaired in rapid viral clearance and in inducing Ag-specific delayed-type hypersensitivity reactions. Thus, the present study demonstrates that down-regulation of CCR7 during CD8 T cell activation is important to release effector cells from the white pulp of the spleen, and highlights the importance of effector cell localization in providing rapid immunity.

Animals↗

PubMed2002

Cutting edge: CCR7+ and CCR7- memory T cells do not differ in immediate effector cell function.

It has been proposed that expression of the chemokine receptor CCR7 represents a defining factor for nonpolarized central (CCR7(+)) and polarized effector memory (CCR7(-)) T cells. In this study, we have tested this hypothesis using in vivo-activated T cells from P14 and SMARTA TCR-transgenic (tg) mice specific for MHC class I- and II-restricted epitopes of the lymphocytic choriomeningitis virus (LCMV) glycoprotein. CCR7 cell surface expression on TCR-tg cells was monitored with a CC chemokine ligand 19-Ig fusion protein. CC chemokine ligand 19-Ig staining separated TCR-tg cells activated by LCMV infection into CCR7(-) and CCR7(+) effector/memory T cell populations. Nonetheless, both T cell populations isolated from spleen and liver produced identical amounts of IFN-gamma after short-term Ag stimulation. Furthermore, CCR7(+) and CCR7(-) CD8 TCR-tg cells from LCMV-infected mice exhibited similar lytic activity against LCMV peptide-coated target cells. These results question the proposed concept of differential effector cell function of CCR7(+) and CCR7(-) memory T cells.

Amino Acid Sequence↗