T cells play a central role in the initiation and regulation of the immune response to foreign antigens. Full activation of T cells requires the engagement of T cell receptor complex (TCR) and the binding of a second costimulatory receptor to its ligand expressed on antigen presenting cells (APC). Among the molecules known to provide costimulatory function, CD28 has been the most dominant and potent costimulatory molecule. However, the function of CD28 is becoming more complex due to the recent discovery of its structural homologue, CTLA-4 and ICOS. This review summarizes the biology and physiologic function of each of these receptors, and further focuses on the biochemical mechanism underlying the function of these receptors. Complete understanding of the CD28/CTLA-4/ICOS costimulatory pathway will provide the basis for developing new therapeutic approaches for immunological dieseases.
Antigen-Presenting Cells ; Biology ; Receptors, Antigen, T-Cell ; T-Lymphocytes

No abstract available.
Hematologic Neoplasms ; Receptors, Antigen, T-Cell

Humans ; Neoplasms ; therapy ; Receptors, Antigen, T-Cell ; T-Lymphocytes

Subcutaneous panniculitis-like T-cell lymphoma(SPTCL) is a rare subtype of cutaneous T-cell lymphoma and needs to be differentiated from benign causes of panniculitis and other cutaneous T-cell lymphomas involving subcutis, especially nasal type NK/T-cell lymphoma(NKTL) involving the panniculus. We report herein two cases of SPTCL which was distinguished from nasal type NKTL by the following findings; CD8+, CD56-, Ebstein Barr virus RNA- and clonal T cell receptor gene arrangement.
Gene Order ; Lymphoma, T-Cell* ; Lymphoma, T-Cell, Cutaneous ; Panniculitis ; Receptors, Antigen, T-Cell ; T-Lymphocytes*

Abstract　　Chimeric antigen receptor-T cell(CAR-T) is a kind of genetically engineered T cells that can express tumor antigen-specific receptors on its surface, and the modified T cells can be used for cancer therapy through targeting malignant tumor cells with its specific receptor and killing tumor cells with its cytotoxicity. CAR-T has been successfully applied to treat various hematological malignancies, such as ALL, CLL, NHL and MM. It is a feasible treatment for relapsed and refractory multiple myeloma (RRMM). The achievements of CAR-T in clinical trials have been widely reported, which is expected to be a therapy to prolong patients survival. In this review, the clinical application of CAR-T in the treatment of RRMM from the following aspects：different types of CAR-T and its curative efficacy, adverse effects, opportunities and challenges are summarized beriefly.
Humans ; Immunotherapy, Adoptive ; Multiple Myeloma ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; T-Lymphocytes

T lymphoid malignancy is a group of highly heterogeneous hematological tumors. Disease recurrence and resistance to therapy are the common causes of failed treatment. Traditional therapy is radiotherapy and chemotherapy, although it has achieved great success. However, many patients still failed to survive following the treatment. With the introduction of monoclonal antibodies, immunotherapy and cellular therapy into clinical practice, the outcome of hematologic malignancies has been significantly improved. In particular, chimeric antigen receptor T cells (CAR-T) showed high efficacy in treating B-cell lymphoma and acute B lymphocytic leukemia and surpassed any previous therapeutic strategies. However, this treatment seldom succeeded in treating T cell malignancies. In this review, the history of CAR-T cells treating T cell malignancies, and the clinical trials, adverse events of previously reported were summarized briefly.
Humans ; Immunotherapy ; Immunotherapy, Adoptive ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; T-Lymphocytes

China ; Consensus ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; T-Lymphocytes

Objective: To explore the efficacy and safety of chimeric antigen receptor T (CAR-T) cells in the treatment of central nervous system leukemia (CNSL). Methods: Two leukemia patients with CNSL were treated with CD19-CAR-T cells. The process and results of the entire treatment is reported and related literature review is conducted. Results: The patients were diagnosed as acute myeloid leukemia (AML)-M(2) with B lymphoid antigen expression and B cell acute lymphoblastic leukemia(B-ALL) by morphology and immunophenotype assay. The immunophenotype was consistent with the abnormal manifestations of AML-M(2) and B-ALL. Their clinical manifestations and laboratory tests met the diagnostic criteria of CNSL. The diagnosis was clear and the two patients were treated with CD19-CAR-T cell immunotherapy. Central nervous system symptoms were relieved. The imaging abnormalities of patient one has disappeared but cytokines release syndrome (CRS) occurred during the treatment. Cerebrospinal fluid of patient two was negative and no obvious CRS reaction was found. Conclusions: CAR-T cell immunotherapy is likely to induce the remission of CNSL and improve the prognosis.
Antigens, CD19 ; Humans ; Immunotherapy, Adoptive ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; T-Lymphocytes

Hematopoietic Stem Cell Transplantation ; Receptors, Antigen, T-Cell

OBJECTIVETo explore the killing effect of CAR (CD138-CD28-CD3ζ)-NK cells on myeloma cells through construction of CAR(CD138-CD28-CD3)-NK cells.

METHODSThe antiCD138scFv-CD28-CD3 zeta plasmid pcDNA3.1 was constructed, which then together with 3 plasmid lentiviral packaging system were transfected into 293T cells, the virus was collected. Furthermore, in order to get the stably transfected cell line, the NK92MI cell line was infected by the virus, then the positive cells were screened by puromycin. The expression of the CARNK cells were verified by RT-PCR and Western blot. At last the ability of secreting cytokine CD107a was detected by flow cytometry, and the statistical analysis was carried out to verify the anti-myeloma effect of CAR-NK cells.

RESULTSGene fragment of the CAR(antiCD138scFv-CD28-CD3ζ) was constructed successfully by gene engineering technique in vitro, and the gene sequence was verified to be correct by sequencing. By virus packaging technology, the virus expressing the protein of the CAR was obtained. PCR and Western blot verified the expression of CAR fusion protein on the sufurce of NK cells. The cell killing experiment confirmed that the CAR-NK cells possessed the ability to secrete cytokine CD107a superior to control cells and showed the obvious killing effect on multiple myeloma cells.

CONCLUSIONThe CAR can be constructed in vitro, and express on NK92 cells. The CAR-NK cells can kill the multiple myeloma cells expressing CD138 antigen, thereby plays an antimyeloma effect.