Human resting B lymphocytes can serve as accessory cells for anti-CD2-induced T cell activation
| Autor: | M, Hirokawa, J D, Gray, T, Takahashi, D A, Horwitz |
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| Rok vydání: | 1992 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes B-Lymphocytes Interleukin-6 CD8 Antigens T-Lymphocytes CD2 Antigens Antigen-Presenting Cells Receptors Fc Intercellular Adhesion Molecule-1 Lymphocyte Activation Lymphocyte Function-Associated Antigen-1 Monocytes Antigens CD Histocompatibility Antigens Humans Leukocyte Common Antigens Receptors Immunologic Cell Adhesion Molecules Interleukin-1 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 149(6) |
| ISSN: | 0022-1767 |
| Popis: | Although resting B cells are poor accessory cells for signals transmitted through the TCR/CD3 complex, we report that these B cells can support T cell proliferation when T cell activating signals are delivered through CD2. This was first suggested when leucine methyl ester treatment of PBMC abolished proliferation induced by anti-CD3, but not by the accessory cell-dependent anti-CD2 mAb combination, GT2 and OKT11. Then we demonstrated that unstimulated, resting B cells could support the proliferation of both CD4+ and CD8+ T cells. Aggregated IgG inhibited proliferation, suggesting that anti-CD2 mAb bound to T cells were cross-linked by attachment to B cell FcR. Two lines of evidence suggested that lymphocyte function-associated Ag-1/intercellular adhesion molecule-1 interaction was crucial for anti-CD2-induced proliferation. First, proliferation was blocked by mAb against these adhesion molecules. Second, intercellular adhesion molecule-1 expression rapidly increased on resting B cells after the addition of anti-CD2, but not anti-CD3. This was of interest because fixed monocytes, but not fixed B cells, were able to support the proliferative response. In contrast to lymphocyte function-associated Ag-1/intercellular adhesion molecule-1, CD28/B7 interaction was not required for anti-CD2-induced proliferation, although ligation of these molecules provided important costimulatory signals for stimulation by anti-CD3. Finally, neutralizing antibodies against IL-1 alpha, IL-1 beta, and IL-6 showed only modest inhibitory effects on T cell proliferation. The addition of IL-1 and/or IL-6 to T cells failed to substitute for accessory cells and were only partially effective with fixed B cells. Further evidence of a linkage between CD2 and CD45 isoforms was obtained. Anti-CD45RA, but not anti-CD45RO, potentiated anti-CD2-induced T cell proliferation. These studies have revealed a novel role for resting B cells as accessory cells and have documented costimulatory signals that are important for this effect. Because Ag-presentation by resting B cells to T cells generally leads to T cell nonresponsiveness, it is possible that this tolerogenic signal may be converted to an activation signal if there is concurrent perturbation of CD2 on T cells. |
| Databáze: | OpenAIRE |
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