Two Separate Mechanisms of T Cell Clonal Anergy to Mls -1a1
Abstract
T cell tolerance to superantigen can be mediated by clonal anergy in which Ag-specific mature T cells are physically present but are not able to mount an immune response. We induced T cell unresponsiveness to minor lymphocyte stimulations locus antigen (Mls)-l a in mice transgenic for TCR V(Sub B)8.1 in three different systems: 1) injection Of MIS-1 a Spleen cells, 2) mating with MlS-la mice, and 3) bone marrow (BM) chimeras in which Mls-1a is present only on nonhematopoietic cells. CD4+8-V(Sub B)8.1 + cells from all these groups did not proliferate in response to irradiated spleen cells from MlS-la mice. We compared the response of these cells by T cell/stimulator cell conjugate formation, Ca2+ mobilization, and proliferation assays. The mechanisms underlying the unresponsiveness of these T cells appear to differ. CD4+8-V(Sub B)38.1 + cells from Mls-la spleen cell-injected mice mobilized cytoplasmic Ca 2 + but proliferated at a reduced level in response to cross-linking with anti-TCR mAb. However, these cells formed conjugates, mobilized Ca 2+ , and proliferated in response to Mls-1 a when activated B cells were used as stimulators, although they produced reduced levels of IL-2. In Mls-1 a/b V (Sub B) 8.1 transgenic mice, a subset in CD4+8-V(Sub B) 8.1 + cells did not mobilize cytoplasmic Ca2+ after TCR cross-linking. Their conjugate formation, Ca 2mobilization, or proliferation in response to Mls-1 a on activated B cells was undetectable. Finally, CD4+8-V(Sub 8) 8.l cells from the BM chimeras proliferated to TCR cross-linking at a partially reduced level and formed conjugates, mobilized Ca2+, and proliferated in response to Mls-la on activated B cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1993
- Accession Number
- ADA273748
Entities
People
- Katsuyuki Kui
- Makoto Katsumata
- Shinji Komori
- Thomas M. Chused
- Yasuo Ishida
Organizations
- Naval Medical Research Center