Biomedical subjects

Yalai Bai

Publications and source records attributed to Yalai Bai.

3 recordsLinked to original sources

PubMed2005

Recruitment of CXCR3+ and CCR5+ T cells and production of interferon-gamma-inducible chemokines in rejecting human arteries.

Chemokine receptors preferentially expressed by Th1 cells and their IFN-gamma-inducible ligands predominate in experimental and clinical allograft rejection. Previous chemokine-related transplantation studies have focused on parenchymal and microvascular inflammation which are of importance in acute rejection, but are not necessarily relevant in immune-mediated injury of conduit arteries. We have recently described a model of progressive human T cell-mediated infiltration and injury of allogeneic coronary artery segments using immunodeficient mouse hosts. In the present study, we investigated if recruitment of allogeneic T cells to different vascular compartments correlated with the expression of chemokines and their receptors. Transcripts were quantified by laser capture microdissection/real-time RT-PCR and their distribution was correlated to the corresponding protein expression detected by immunohistochemistry. Infiltrating T cells, confined to the adventitia and intima, expressed CXCR3 and CCR5, but were not recruited into the media despite production by vascular smooth muscle cells of IP-10, Mig, I-TAC, RANTES and MIP-1beta. Chemokine mRNA was detected primarily in vascular cells, although chemokine protein largely localized to infiltrating leukocytes which uniquely expressed their cognate receptors. These data explain the recruitment of IFN-gamma-secreting T cells to the vessel wall, and reinforce the suggestion that the arterial media may be a site of immunological privilege.

Antineoplastic Agents↗

PubMed2002

L-selectin-dependent lymphoid occupancy is required to induce alloantigen-specific tolerance.

Maneuvers that interfere with signals 1, 2, 3, or Ag processing can result in indefinite allograft survival. However, they are not applicable to all tissues, strains, or species, suggesting that there are additional levels of immune regulation. We hypothesized that secondary lymphoid organs are important for interactions among lymphocytes, alloantigen, and immunosuppressants that lead to tolerance. To explore this, cardiac allografts were performed with a tolerogenic immunosuppressive regimen. Concurrent administration of anti-L-selectin (CD62L) Ab, which prevents lymph node homing, prevents indefinite allograft survival and tolerance. Anti-CD62L Ab is not costimulatory, and Fab and F(ab')(2) anti-CD62L have similar activities. Flow cytometry and histologic examination show that Ab shifts T cells away from lymph nodes and into spleen, peripheral blood, and graft. Tolerance is not induced in CD62L(-/-) mice, and adoptive transfer of CD62L(-/-), but not CD62L(+/+), T cells prevents tolerization in wild-type recipients. FTY720, an immunosuppressant that promotes chemokine-dependent, but CD62L-independent, lymph node homing, reverses the Ab effect. Blockade of other homing receptors also prevents tolerization. These results indicate that T lymphocytes use CD62L-dependent migration for alloantigen-specific tolerance, and suggest that lymph nodes or other lymphoid tissues are an important site for peripheral tolerization to alloantigen.

Animals↗

PubMed2002

CD2 is a dominant target for allogeneic responses.

CD2 and 2B4 (CD244) are members of the immunoglobulin gene superfamily and are both ligands for another family member, CD48. CD2 is widely distributed on T, NK, and B cells and some antigen-presenting cells, while 2B4 is expressed on NK and some T cells and monocytes and is known to participate in NK cytotoxicity. Since indefinite allograft survival could be obtained by a combination of anti-CD48 plus anti-CD2 mAb administration, it was important to determine the role of 2B4 blockade in allograft rejection. MAbs directed against CD2, CD48, or 2B4 were administered singly or in pairs to cardiac allograft recipients. The experiments show that only anti-CD2 plus anti-CD48 mAbs result in indefinite allograft survival, while anti-CD2 plus anti-2B4 mAbs substantially prolong graft survival, and anti-CD48 plus anti-2B4 mAbs were no better than each mAb alone. The effect of these mAbs on anti-CD3 mAb and alloantigen-driven proliferation and IFN-gamma production were also assessed. In general, anti-CD2 inhibited both anti-CD3 mAb and alloantigen-driven responses, while anti-CD48 inhibited only anti-CD3 mAb but not alloantigen-driven proliferative and cytokine responses. Anti-2B4 mAbs were generally ineffective alone. Combinations of mAbs were more effective than single mAbs only in alloantigen-driven proliferation, commensurate with allograft survival results. Using CD2-/- and CD48-/- T cells and antigen-presenting cells, we also demonstrate that these inhibitory mAbs act primarily by blocking intercellular interactions, rather than directly delivering negative signals to T cells. These results suggest that, unlike CD2, 2B4 is not a potent regulatory molecule or ligand for CD48 in the response to alloantigen. Blocking the 2B4-CD48 receptor-ligand pair does not inhibit T-cell responses and alloreactivity to the same degree as CD2-CD48 blockade.

Animals↗