2019 coronavirus disease (COVID‐19) presents as a newly recognized pneumonia and could rapidly progress into acute respiratory distress syndrome which has brought about a global pandemic. Until now, no curative therapy has been strongly recommended for COVID‐19 except for personalized supportive care. T cells and virus‐specific T cells are essential to protect against virus infection, including COVID‐19. Delayed immune reconstitution (IR) and cytokine storm (CS) remain serious obstacles for the cure of COVID‐19. Most COVID‐19 patients, especially among elderly patients, had marked lymphopenia and increased neutrophils, but T cell counts in severe COVID‐19 patients surviving the disease gradually restored later. Elevated pro‐inflammatory cytokines, particularly IL‐6, IL‐10, IL‐2 and IL‐17, and exhausted T cells are found in peripheral blood and the lungs. It suggests that Thymosin α1 and adoptive COVID‐19‐specific T cells could improve IR, while convalescent plasma, IL‐6 blockade, mesenchymal stem cells and corticosteroids could suppress CS. More clinical studies in this field worldwide are urgently warranted to pave the way for therapy of COVID‐19 in the future.

Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i.e., NY-ESO-1, Survivin or EGFRvIII). TILs were analyzed by flow cytometry, including T-cell receptor (TCR) Vβ family composition, exhaustion/activation and T-cell differentiation markers (CD45RA/CCR7). IL-2/IL-15/IL-21 expanded TILs exhibited a mixture of CD4⁺, CD8⁺, as well as CD3⁺ CD4⁻CD8⁻ T cells with a predominant central memory CD45RA⁻CCR7⁺ phenotype. TIL showed low frequencies of T cells testing positive for PD-1, TIM-3 and CTLA-4. LAG3 tested positive in up to 30% of CD8⁺ TIL, with low (1.25%) frequencies in CD4⁺ T cells. TIL cultures exhibited preferential usage of Vβ families and recognition of autologous tumor cells defined by cytokine production and cytotoxicity. IL-2/IL-15/IL-21 expanded TILs represent a viable source for the cellular therapy of patients with gliomas.

Human cytomegalovirus (CMV)-specific cytotoxic T lymphocyte (CTL) immune response must be reconstituted for long-term protection against CMV relapse and disease in hematopoietic stem cell transplantation (HSCT) recipients. We phenotypically quantitated absolute numbers of CMV-pp65 peptide-specific CTLs (CTL(CMV)) in 50 related donor unmanipulated allografts infused into HLA-matched or -mismatched recipients and examined the incidence of CMV reactivation. High CTL(CMV) with terminally differentiated effector CD45RO(-)CD62L(-) cell (T(EMRA)) phenotype in the allografts were associated with reduced risk of CMV reactivation, in the presence of sufficient CD45RO(+)CD62L(-) cell (T(EM)) infusion (>/=0.208 x 10(6)/kg). Early after transplantation, there was significant expansion of CTL(CMV) with the central memory CD45RO(+)CD62L(+) cell (T(CM)) phenotype when CMV was reactivated. The frequencies of CTL(CMV) T(Naive) (CD45RO(-)CD62L(+)), T(CM), and T(EM) at day 90 posttransplantation and of CTL(CMV) T(EMRA) at day 60 posttransplantation were greater in recipients with higher infusions of CTL(CMV) T(EMRA), suggesting protective immunity transferred by infusion of CTL(CMV) within allografts. Moreover, the majority of the CTL(CMV) identified in the recipients early after HSCT was of donor origin. Our findings support that measuring levels of CTL(CMV) and its subsets in the donor grafts and manipulating these cells early after transplantation may help control CMV reactivation, which is closely correlated with immune reconstitution and differentiation of CTL(CMV) subsets.

Haploidentical stem cell transplantation (haploSCT) has advanced to a common procedure for treating patients with hematological malignancies and immunodeficiency diseases. However, cure is seriously hampered by cytomegalovirus (CMV) infections and delayed immune reconstitution for the majority of haploidentical transplant recipients compared to HLA-matched stem cell transplantation. Three major approaches, includingin vivoT-cell depletion (TCD) using antithymocyte globulin for haploSCT (in vivoTCD-haploSCT),ex vivoTCD using CD34 + positive selection for haploSCT (ex vivoTCD-haploSCT), and T-cell replete haploSCT using posttransplant cyclophosphamide (PTCy-haploSCT), are currently used worldwide. We provide an update on CMV infection and CMV-specific immune recovery in this fast-evolving field. The progress made in cellular immunotherapy of CMV infection after haploSCT is also addressed. Groundwork has been prepared for the creation of personalized avenues to enhance immune reconstitution and decrease the incidence of CMV infection after haploSCT.