Differential MHC expression requirements for positive selection of separate TCR Vb families

• Positive selection has been proposed to be involved in protection from diabetes. We examined positive selection by fluorescence-activated cell sorter analyses in thymocytes of protected and susceptible E-transgenic and non-transgenic NOD mice. Three Vb families showed positive selection in E-transgenic mice. Vb6+CD4+ and Vb10+CD4+ thymocytes were found at higher frequencies in both protected NOD-Ea and susceptible NOD-DY mice. The increased frequencies of Vb13+CD8+ thymocytes were found in protected NOD-Ea mice only, and not in susceptible NOD-DY transgenic mice. These three Vb families were further examined in bone-marrow chimeras between NOD-Ea and non-transgenic NOD mice, where we could examine the contribution of E-expressing bone-marrow-derived cells in positive selection. We find that NOD-Ea→NOD-Ea chimeras have an increased positive selection of Vb13+CD8+ cells and that positive selection is more efficient when both thymic epithelium and bone-marrow-derived cells express the E molecule. This was also seen for Vb6+CD4+ cells. However, for Vb6, bone-marrow-derived cells alone were also capable of positive selection. Positive selection of Vb10+CD4+ cells was restricted to E-expressing thymic epithelium only. For Vb13+CD8+ cells, we found that positive selection is most efficient with E-expression on both thymic epithelium and bone-marrow-derived cells, although positive selection also occurs with E-positive epithelium only. For Vb6+CD4+ cells, the dominating selecting cells are bone-marrow-derived cells, and Vb10+CD4+ cells seem to be selected exclusively by the thymic epithelium. Thus, the conditions for positive selection seem to vary considerably between different Vb families.

Ämnesord

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

Nyckelord

Bone marrow

Postive selection

Thymic epithelium

Vb-NOD

cd4 antigen

cd8 antigen

major histocompatibility antigen

t lymphocyte receptor

animal cell

animal experiment

antigen expression

article

bone marrow cell

cell selection

chimera

controlled study

diabetes mellitus

fluorescence activated cell sorter

genetic susceptibility

mouse

nonhuman

priority journal

thymocyte

transgenic mouse

Animals

Autoimmune Diseases

Bone Marrow Cells

Bone Marrow Transplantation

CD4-Positive T-Lymphocytes

CD8-Positive T-Lymphocytes

Clonal Deletion

Diabetes Mellitus

Type 1

Female

Gene Rearrangement

beta-Chain T-Cell Antigen Receptor

Histocompatibility Antigens Class II

Mice

Mice

Inbred C57BL

Mice

Inbred NOD

Mice

Transgenic

Radiation Chimera

Receptors

Antigen

T-Cell

alpha-beta

T-Lymphocyte Subsets

Thymus Gland

Animalia

Mus musculus

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)