Dasatinib Has a Dual Mode of Action: Direct BCR-ABL1 Mediated Anti-Leukemic Effects Are Complemented by Promotion of Th1-Type and NK-Cell Mediated Cellular Immune Responses,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3760-3760 ◽  
Author(s):  
Anna Kreutzman ◽  
Jukka Vakkila ◽  
Kimmo Porkka ◽  
Satu Mustjoki
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
K562 Cells ◽  
Leukemic Cells ◽  
Healthy Controls ◽  
Median Percentage ◽  
Blood Smears ◽  
Cellular Immune

Abstract Abstract 3760 Background. Tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib) have dramatically improved outcome of CML. Besides inhibiting target kinases in leukemic cells, off-target kinases in immune effector cells are also affected. We have previously described that dasatinib therapy induces an oligoclonal expansion and mobilization of large granular lymphocytes (LGLs; CD8+ T-cells or NK-cells) in Ph+ leukemia patients. Importantly, LGL expansion is associated with improved therapy responses, but the actual mechanisms are unknown. In this study, we explored the function and anti-leukemic properties of LGLs. Methods. Peripheral blood samples from CML patients treated with dasatinib (n=10), imatinib (n=4), or nilotinib (n=7), or healthy controls (n=6) were used to analyze the activation and cytotoxicity of T- and NK-cells. Samples were collected before and after drug intake. The number of LGLs was determined from MGG stained blood smears and compared with granzyme B (GrB) positivity analyzed by flow cytometry. Th1-type cytokine (TNF-a, IFN-g) production was measured by flow cytometry after stimulation of mononuclear cells (MNCs) with a-CD3/CD28-antibodies. Unpurified and purified NK cells were cultured with K562 cells, and degranulation (CD107 analysis) and cytotoxicity were measured. Results. As GrB positivity correlated well (r=0.95, p<0.0001, n=17) with the number of LGLs counted from MGG stained blood smears, a GrB specific antibody was used to identify LGLs in further analyses. At diagnosis CML patients had more GrB+CD8+ T-cells than healthy controls (38 % vs. 11%, p=0.028). Also GrB+CD4+ T-cells were slightly increased, but did not differ significantly from healthy controls (3.6% vs. 0.8%, p=0.08). During dasatinib treatment the proportion of GrB+CD4+ (median at 6 months 28.1%, p=0.03) and GrB+CD8+ (70.9%, p=0.03) T cells increased significantly, whereas similar increase was not observed during imatinib (1.2% GrB+CD4+ and 30.0% GrB+CD8+ T-cells) or nilotinib (4.4% and 41.8%, respectively) therapies. In patients on dasatinib therapy, GrB+CD3+cells were more sensitive to CD3/CD28-antibody stimulation and a larger proportion of cells (13.7%) produced Th1-type cytokines (TNF-a+IFN-g) compared to imatinib (2.4%) or nilotinib patients (5.5%) or healthy controls (5%) under same conditions (p=0.015). As Th-1 cytokine-producing T cells are important in promoting cell-mediated immune responses, we next assessed whether dasatinib also enhances the cytolytic activity of NK cells. When MNC fraction was used as effector population (ratio 20:1), the median percentage of dead K562 cells was 18% in samples taken before dasatinib intake and 32% in samples taken 1h after dasatinib intake (p=0.004). Pre-dasatinib killing did not differ significantly from healthy volunteers (p=0.12). No increase in NK-cytotoxicity was observed after imatinib (11% vs. 8%) or nilotinib (10% vs. 10%) intake. Similar results were also obtained with purified NK-cells: the median percentage of dead K562 cells was 12% pre-dasatinib and 29% in post-dasatinib samples (p=0.06), whereas no differences were noticed with imatinib (30% vs. 28%) or nilotinib (14% vs. 15%) patients. The median percentage of dead K562 cells after incubation with pure NK-cells from healthy volunteers was 20%. Interestingly, the cytolytic ability of NK-cells differed significantly among dasatinib treated patients. When the patients were divided into two groups based on therapy response, patients who had achieved CMR within 12 months (n=4) had significantly higher cytotoxic capability compared to patients who had not (n=6): 46% vs. 28% of dead K562 cells in post-dasatinib samples (p=0.02). Conclusions. Dasatinib therapy resulted in increased numbers of GrB+ T-cells and generation of a Th1-type cellular immune response. In addition, 1h dasatinib exposure in vivo improved the cytotoxicity of NK-cells. These data support the dual mode of action of dasatinib: potent BCR-ABL1 inhibition in leukemic cells is accompanied by enhancement of cellular immunity, which likely have implications in be the long term control of Ph+ leukemia. Disclosures: Porkka: Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Mustjoki:Bristol-Myers Squibb: Honoraria; Novartis: Honoraria.

MIP-1α and MIP-1β differentially mediate mucosal and systemic adaptive immunity

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 807-814 ◽  
Author(s):  
James W. Lillard ◽  
Udai P. Singh ◽  
Prosper N. Boyaka ◽  
Shailesh Singh ◽  
Dennis D. Taub ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Cd8 T Cells ◽  
Host Cells ◽  
Secretory Iga ◽  
Specific Cell ◽  
Cellular Immune Responses ◽  
Cc Chemokines ◽  
Cellular Immune

AbstractMacrophage inflammatory protein-1α (MIP-1α) and MIP-1β are distinct but highly homologous CC chemokines produced by a variety of host cells in response to various external stimuli and share affinity for CCR5. To better elucidate the role of these CC chemokines in adaptive immunity, we have characterized the affects of MIP-1α and MIP-1β on cellular and humoral immune responses. MIP-1α stimulated strong antigen (Ag)–specific serum immunoglobulin G (IgG) and IgM responses, while MIP-1β promoted lower IgG and IgM but higher serum IgA and IgE antibody (Ab) responses. MIP-1α elevated Ag-specific IgG1 and IgG2b followed by IgG2a and IgG3 subclass responses, while MIP-1β only stimulated IgG1 and IgG2b subclasses. Correspondingly, MIP-1β produced higher titers of Ag-specific mucosal secretory IgA Ab levels when compared with MIP-1α. Splenic T cells from MIP-1α– or MIP-1β–treated mice displayed higher Ag-specific Th1 (interferon-γ [IFN-γ]) as well as selective Th2 (interleukin-5 [IL-5] and IL-6) cytokine responses than did T cells from control groups. Interestingly, mucosally derived T cells from MIP-1β–treated mice displayed higher levels of IL-4 and IL-6 compared with MIP-1α–treated mice. However, MIP-1α effectively enhanced Ag-specific cell-mediated immune responses. In correlation with their selective effects on humoral and cellular immune responses, these chemokines also differentially attract CD4+ versus CD8+ T cells and modulate CD40, CD80, and CD86 expressed by B220+ cells as well as CD28, 4-1BB, and gp39 expression by CD4+ and CD8+ T cells in a dose-dependent fashion. Taken together, these studies suggest that these CC chemokines differentially enhance mucosal and serum humoral as well as cellular immune responses.

scholarly journals Human Ebola virus infection results in substantial immune activation

2015 ◽  
Vol 112 (15) ◽  
pp. 4719-4724 ◽  
Author(s):  
Anita K. McElroy ◽  
Rama S. Akondy ◽  
Carl W. Davis ◽  
Ali H. Ellebedy ◽  
Aneesh K. Mehta ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Immune Activation ◽  
Ebola Virus ◽  
Natural Infection ◽  
University Hospital ◽  
Cellular Immune ◽  
Ebola Virus Infection

Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

scholarly journals Hepatic cellular immune responses in mice with “cure” and “non-cure” phenotype toLeishmania infantuminfection: importance of CD8+T cells and TGF-β production

2004 ◽  
Vol 41 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Sandra Gomes-Pereira ◽  
Olivia Roos Rodrigues ◽  
Nuno Rolão ◽  
Paulo David Almeida ◽  
Gabriela Maria Santos-Gomes
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Using Natural Adjuvants to Stimulate Anti-Tumour Immune Responses

2021 ◽  
Author(s):  
◽  
Sabine Kuhn
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Tumour Growth ◽  
Tumour Site ◽  
Effector Cells ◽  
Draining Lymph Nodes

<p><b>The anti-tumour immune response is often not potent enough to prevent or eradicate disease. Dendritic cells (DCs) are professional antigen-presenting cells that are critical for the initiation of immune responses. While DCs frequently infiltrate tumours, lack of activation together with immuno-suppressive factors from the tumour can hamper an effective anti-tumour immune response.</b></p> <p>In this thesis, the ability of microbial stimuli and danger signals to overcome suppression and re-programme DCs and macrophages to an immuno-stimulatory phenotype was investigated. Whole live Mycobacterium smegmatis and BCG were used to provide multiple pathogen-associated molecular patterns. The intracellularly-recognised toll-like-receptor (TLR) ligands CpG and Poly IC, as well as the extracelullarly recognised TLR ligand LPS, and the danger signal monosodium-urate crystals (MSU) were also included.</p> <p>Bone-marrow derived DCs were found to respond to all adjuvants in vitro and DCs in tumour cell suspensions could be activated ex vivo. To assess the ability of adjuvants to enhance anti-tumour responses in vivo, immune-competent mice bearing established subcutaneous B16F1 melanomas were injected peri-tumorally with the different adjuvants. In line with previous reports, CpG treatment was effective in delaying tumour growth and increasing survival. A similar effect was found with Poly IC, but not with LPS, M. smegmatis, BCG or MSU alone. Combination of M. smegmatis + MSU, however, significantly delayed tumour growth and prolonged survival, while combinations of MSU + BCG or LPS were ineffective. Similar results were obtained using the B16.OVA melanoma and E.G7-OVA thymoma subcutaneous tumour models. In addition, Poly IC and MSU + M. smegmatis reduced primary tumour growth as well as lung metastases in the orthotopic 4T1 breast carcinoma model.</p> <p>Both Poly IC and MSU + M. smegmatis elicited an anti-tumour immune response that required CD8 T cells as well as NK cells. These treatments also resulted in increased proliferation of CD8 T cells and NK cells in tumour-draining lymph nodes, augmented infiltration of effector cells into the tumour, as well as enhanced production of in ammatory cytokines by effector cells and DCs in tumours. In addition, MSU + M. smegmatis also stimulated CD4 T cell proliferation, tumour-infiltrationand activation, while at the same time decreasing the frequency of regulatory T cells in tumours.</p> <p>Activation of a successful immune response to tumours was associated with early induction of IL-12 and IFNʸ, as well as moderate levels of pro-inflammatory cytokines at the tumour site and systemically. Furthermore, anti-tumour activity correlated with the induction of inflammatory monocyte-derived DCs in tumour-draining lymph nodes. These DCs were also observed in adjuvant treated tumours and their appearance was preceded by accumulation of inflammatory monocytes at the tumour site.</p> <p>These findings suggest that specific natural adjuvants can successfully modify the tumour environment and enhance the innate and adaptive anti-tumour immune response to delay tumour progression and increase survival.</p>

scholarly journals Immune characterization of a Colombian familiar cluster of SARS-CoV-2 infection

Biomédica ◽  
2021 ◽  
Vol 41 (Sp. 2) ◽  
Author(s):  
Wbeimar Aguilar-Jiménez ◽  
Lizdany Flórez-Álvarez ◽  
Daniel S. Rincón ◽  
Damariz Marín-Palma ◽  
Alexandra Sánchez-Martínez ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
K562 Cells ◽  
Neutralization Assay ◽  
Immunological Markers ◽  
Hla Dr ◽  
Immune Alterations ◽  
And Function

Introduction: Immunological markers have been described during COVID-19 and persist after recovery. Those immune alterations are associated with clinical features among SARS-CoV-2 infected individuals. Although, studies reporting a comprehensive analysis of these immune alterations are still limited. Objective: To evaluate the production of pro-inflammatory cytokines, antibody response, and phenotype and function of NK cells and T cells in a Colombian familiar cluster of SARS-CoV-2 infection. Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. Frequency, phenotype and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with Spike/RdRp peptides) were assessed by flow cytometry; anti-SARS-CoV-2 antibodies were determined by indirect immunofluorescence and plaque reduction neutralization assay. Results: During COVID-19, we observed a high pro-inflammatory cytokine production and reduced CD56bright NK cells and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by a high IL-10 production. Nevertheless, during recovery, a bifunctional response was observed, characterized by the co-expression of CD107a and Granzyme B or Perforin. Conclusion: Although pro-inflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and, to guide future immunotherapy strategies. 

scholarly journals Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19

2020 ◽  
Author(s):  
Hasi Chaolu ◽  
Xinri Zhang ◽  
Xin Li ◽  
Xin Li ◽  
Dongyan Li
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Subsets ◽  
Healthy Controls ◽  
Tnf Α ◽  
Ifn Γ ◽  
Circulating Cytokines

To investigate the immune status of people who previously had COVID-19 infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%) and IL-17 (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

scholarly journals A highly specific assay for the detection of SARS-CoV-2-reactive CD4+ and CD8+ T cells in COVID-19 patients

2020 ◽  
Author(s):  
Henning Zelba ◽  
David Worbs ◽  
Johannes Harter ◽  
Natalia Pieper ◽  
Christina Kyzirakos-Feger ◽  
...  
Keyword(s):  
T Cells ◽  
Membrane Protein ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Functional Markers ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Gaining detailed insights into the role of host immune responses in viral clearance is critical for understanding COVID-19 pathogenesis and future treatment strategies. While studies analyzing humoral immune responses against SARS-CoV-2 were available rather early during the pandemic, cellular immunity came into focus of investigations just recently. For the present work, we have adapted a protocol, designed for the detection of rare neoantigen-specific Memory T cells in cancer patients for studying cellular immune responses against SARS-CoV-2. Both, CD4+ and CD8+ T cells were detected after 6 days of in vitro expansion using overlapping peptide libraries representing the whole viral protein. The assay readout was an Intracellular cytokine staining and flow cytometric analysis detecting four functional markers simultaneously (CD154, TNF, IL-2, IFN-γ). We were able to detect SARS-CoV-2-specific T cells in 9 of 9 COVID-19 patients with mild symptoms. All patients had reactive T cells against at least one of 12 analyzed viral antigens and all patients had Spike-specific T cells. While some antigens were detected by CD4+ and CD8+ T cells, Membrane protein was mainly recognized by CD4+ T cells. Strikingly, we were not able to detect SARS-CoV-2-specific T cells in 9 unexposed healthy individuals. We are presenting a highly specific protocol for the detection of SARS-CoV-2-reactive T cells. Our data confirmed the important role of cellular immune responses in understanding SARS-CoV-2 clearance. We showed that Spike is the most immunogenic antigen. We have introduced Membrane protein as interesting target for studying humoral immune responses in convalescent COVID-19 patients.

The NK and NKT Cell Compartment Is Suppressed in CML Patients before and after Imatinib Treatment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4667-4667
Author(s):  
Christiane I.-U. Chen ◽  
Holden Maecker ◽  
Peter P. Lee
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Imatinib Mesylate ◽  
Cd8 T Cells ◽  
Lymphocyte Subsets ◽  
Nkt Cells ◽  
Healthy Controls ◽  
Nkt Cell ◽  
Cell Counts ◽  
Before And After

Abstract In CML patients, lymphocyte subsets have been shown to be disturbed. NK cells as well as CD8+ T cells have been shown to be significantly lower in patients with relapse after BMT than without relapse (Jiang et al., 1996). After successful treatment (IFN- α and BMT/SCT), MHC-restricted CD8+ T cells as well as MHC-unrestricted cytotoxic NK and lymphokine activated killer (LAK) cells play an important role in controlling the disease (Meseri et al., 1993, de Castro et al., 2003, Molldrem et al., 2000), which can lead not only to hematological, but also cytogenetic responses. The development of imatinib mesylate, a selective inhibitor of the bcr/abl tyrosine kinase, as a first-line therapy enormously enhanced treatment options for CML patients, and has led to hematologic, and occasionally cytogenetic, responses at various stages of disease. To explore, if CML patients, who develop clinical responses with imatinib mesylate treatment, have normalization of their lymphocyte subsets with restoration of CD8+ and NK cells, we studied peripheral blood T cell, B cell, and NK cell subpopulations in patients in chronic or accelerated phase before and after treatment with imatinib mesylate. In 5 CML patients, 8-color flow cytometry was applied to investigate the lymphocyte subsets using anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD56, anti-CD25, anti-CD27, and anti-CD45RA antibodies. 5 healthy donors served as controls. There was no significant difference in CD19+ B cells or CD3+ T cells as well as its CD4+ and CD8+ subsets between CML patients and healthy controls. T regulatory cells (CD4+CD25+) were also similar in patients in comparison to the healthy controls (0.6% – 3% vs 2.3%). In contrast, CD3–CD56+ NK cells (4% vs 14%, p&lt;0.05) as well as NK T cells (CD3+CD56+ 1% vs 14%, p&lt;0.02; CD8+CD56+ 2% vs 17%, p&lt;0.03) were profoundly decreased in CML patients compared to the healthy controls prior to treatment with imatinib mesylate. Importantly, these abnormalities persisted even during treatment and following hematological responses (range 10 months – 35 months) (CD3-CD56+ 4–8%, CD3+CD56+ 0.5–5.5%, CD8+CD56+ 2.7–7%). On further analysis, these NK and NKT cells were mostly effector (CD45RA+CD27−, 50–80%) or memory (CD45RA-CD27+, 10–30%) cells. These results suggest, that CML not only disturbs the myeloid and the lymphoid compartment before treatment, but persistently impairs the MHC-unrestricted cytotoxic NK cells and NKT cells after treatment with imatinib mesylate, even in patients in hematological (and cytogenetic) remission with normal white cell counts (2.0 – 8.0/nl). Further investigations are required to better understand the mechanism of the prolonged and specific NK and NKT cell suppression in imatinib mesylate treated patients, and its impact on the course of the disease.

scholarly journals Circulating Cytokines and Lymphocyte Subsets in Patients Who Have Recovered from COVID-19

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Hasichaolu ◽  
Xinri Zhang ◽  
Xin Li ◽  
Xin Li ◽  
Dongyan Li
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Subsets ◽  
Healthy Controls ◽  
Cell Counts ◽  
Tnf Α ◽  
Ifn Γ

To investigate the immune status of people who previously had COVID-19 infections, we recruited two-week postrecovery patients and analyzed circulating cytokine and lymphocyte subsets. We measured levels of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells and the serum concentrations of interleukin- (IL-) 1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most postrecovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8+ T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells (51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%), and IL-17 (97.06%). Compared to healthy controls, two-week postrecovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17. Among postrecovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells were positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, postrecovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system gradually recovers following COVID-19 infection; however, the sustained hyperinflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

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