Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors

AbstractIdiopathic CD4+ lymphocytopenia (ICL) is a rare non–HIV-related syndrome with unclear natural history and prognosis. This prospective natural history cohort study describes the clinical course, CD4 T lymphocyte kinetics, outcome, and prognostic factors of ICL. Thirty-nine patients (17 men, 22 women) 25 to 85 years old with ICL were evaluated between 1992 and 2006, and 36 were followed for a median of 49.5 months. Cryptococcal and nontuberculous mycobacterial infections were the major presenting opportunistic infections. Seven patients presented with no infection. In 32, CD4 T-cell counts remained less than 300/mm3 throughout the study period and in 7 normalized after an average of 31 months. Overall, 15 (41.6%) developed an opportunistic infection in follow-up, 5 (13.8%) of which were “AIDS-defining clinical conditions,” and 4 (11.1%) developed autoimmune diseases. Seven patients died, 4 from ICL-related opportunistic infections, within 42 months after diagnosis. Immunologic analyses revealed increased activation and turnover in CD4 but not CD8 T lymphocytes. CD8 T lymphocytopenia (< 180/mm3) and the degree of CD4 T cell activation (measured by HLA-DR expression) at presentation were associated with adverse outcome (opportunistic infection-related death; P = .003 and .02, respectively). This trial is registered at http://clinicaltrials.gov as #NCT00001319.

Download Full-text

Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function

Clinical Immunology ◽

10.1016/j.clim.2006.04.570 ◽

2006 ◽

Vol 120 (2) ◽

pp. 163-170 ◽

Cited By ~ 42

Author(s):

Sonia Fernandez ◽

Patricia Price ◽

Elizabeth J. McKinnon ◽

Richard C. Nolan ◽

Martyn A. French

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

T Cell Activation ◽

Cell Activation ◽

Cell Function ◽

Cd4 T Cell ◽

Effector Memory ◽

Hiv Patients ◽

Memory T Cell ◽

Cell Counts

Download Full-text

Suppressive activity of regulatory T cells correlates with high CD4+ T-cell counts and low T-cell activation during chronic simian immunodeficiency virus infection

AIDS ◽

10.1097/qad.0b013e3283437c7b ◽

2011 ◽

Vol 25 (5) ◽

pp. 585-593 ◽

Cited By ~ 6

Author(s):

Ingrid Karlsson ◽

Benoît Malleret ◽

Patricia Brochard ◽

Benoît Delache ◽

Julien Calvo ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Virus Infection ◽

Regulatory T Cells ◽

T Cell Activation ◽

Cell Activation ◽

Cd4 T Cell ◽

Suppressive Activity ◽

Cell Counts ◽

Immunodeficiency Virus

Download Full-text

Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV-1

10.1101/2021.09.14.21263556 ◽

2021 ◽

Cited By ~ 1

Author(s):

Yanmeng Feng ◽

Yifan Zhang ◽

Zhangyufan He ◽

Haojie Huang ◽

Xiangxiang Tian ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Cd8 T Cell ◽

Cd4 T Cell ◽

People Living With Hiv ◽

Healthy Individuals ◽

Cell Counts ◽

Living With Hiv ◽

Hiv 1

Background It has been proven that inactivated COVID-19 vaccines are safe and effective in general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH). Methods 42 HIV-1 infected individuals who were stable on cART and 28 healthy individuals were enrolled in this study. Two doses of an inactivated COVID-19 vaccine (BIBP-CorV) were given 4 weeks apart. The safety and reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry. Findings All the HIV-1 infected participants had a CD4+ T cell count of above 200 cells/μL both at baseline and 4 weeks after vaccination. No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. Further analyses showed that PLWH with low baseline CD4+/CD8+ T cell ratios (<0.6) generated lower antibody responses after vaccination than PLWH with medium (0.6~1.0) or high (≥1.0) baseline CD4+/CD8+ T cell ratios (P<0.01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination, but it did not lead to any adverse clinical manifestation. Moreover, we found that the general burden of HIV-1 among the PLWH cohort decreased significantly (P=0.0192) after vaccination. And the alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation. Interpretation Our data demonstrate that the inactivated COVID-19 vaccine is safe and immunogenic in PLWH who are stable on cART with unsuppressed CD4 counts. Funding This work was funded by the National Natural Science Foundation of China (Grant No. 81971559, 82041010).

Download Full-text

COVID-19 in multiple-myeloma patients: cellular and humoral immunity against SARS-CoV-2 in a short- and long-term view

Journal of Molecular Medicine ◽

10.1007/s00109-021-02114-x ◽

2021 ◽

Author(s):

Ivana von Metzler ◽

Julia Campe ◽

Sabine Huenecke ◽

Marc S. Raab ◽

Hartmut Goldschmidt ◽

...

Keyword(s):

Multiple Myeloma ◽

Immune Response ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Tumor Therapy ◽

Cd4 T Cell ◽

List Type ◽

Cell Counts ◽

Antibody Titers

Abstract Multiple myeloma patients are often treated with immunomodulatory drugs, proteasome inhibitors, or monoclonal antibodies until disease progression. Continuous therapy in combination with the underlying disease frequently results in severe humoral and cellular immunodeficiency, which often manifests in recurrent infections. Here, we report on the clinical management and immunological data of three multiple-myeloma patients diagnosed with COVID-19. Despite severe hypogammaglobulinemia, deteriorated T cell counts, and neutropenia, the patients were able to combat COVID-19 by balanced response of innate immunity, strong CD8+ and CD4+ T cell activation and differentiation, development of specific T-cell memory subsets, and development of anti-SARS-CoV-2 type IgM and IgG antibodies with virus-neutralizing capacities. Even 12 months after re-introduction of lenalidomide maintenance therapy, antibody levels and virus-neutralizing antibody titers remained detectable, indicating persisting immunity against SARS-CoV-2. We conclude that in MM patients who tested positive for SARS-CoV-2 and were receiving active MM treatment, immune response assessment could be a useful tool to help guide decision-making regarding the continuation of anti-tumor therapy and supportive therapy. Key messages Immunosuppression due to multiple myeloma might not be the crucial factor that is affecting the course of COVID-19. In this case, despite pre-existing severe deficits in CD4+ T-cell counts and IgA und IgM deficiency, we noticed a robust humoral and cellular immune response against SARS-CoV-2. Evaluation of immune response and antibody titers in MM patients that were tested positive for SARS-CoV-2 and are on active MM treatment should be performed on a larger scale; the findings might affect further treatment recommendations for COVID-19, MM treatment re-introduction, and isolation measures.

Download Full-text

Human Herpesvirus Replication and Abnormal CD8+ T Cell Activation and Low CD4+ T Cell Counts in Antiretroviral-Suppressed HIV-Infected Patients

PLoS ONE ◽

10.1371/journal.pone.0005277 ◽

2009 ◽

Vol 4 (4) ◽

pp. e5277 ◽

Cited By ~ 17

Author(s):

Mark A. Jacobson ◽

Dirk P. Ditmer ◽

Elizabeth Sinclair ◽

Jeffrey N. Martin ◽

Steven G. Deeks ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Human Herpesvirus ◽

Cd8 T Cell ◽

Cd4 T Cell ◽

Cell Counts

Download Full-text

Normal T-cell activation in elite controllers with preserved CD4+ T-cell counts

AIDS ◽

10.1097/qad.0000000000000860 ◽

2015 ◽

Vol 29 (17) ◽

pp. 2245-2254 ◽

Cited By ~ 15

Author(s):

Anju Bansal ◽

Sarah Sterrett ◽

Nathan Erdmann ◽

Andrew O. Westfall ◽

Jodie Dionne-Odom ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Cd4 T Cell ◽

Elite Controllers ◽

Cell Counts

Download Full-text

Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection

Blood ◽

10.1182/blood-2006-09-047308 ◽

2006 ◽

Vol 109 (7) ◽

pp. 2912-2920 ◽

Cited By ~ 48

Author(s):

Marie-Lise Dion ◽

Rebeka Bordi ◽

Joumana Zeidan ◽

Robert Asaad ◽

Mohammed-Rachid Boulassel ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Disease Progression ◽

T Cell Activation ◽

Cd4 T Cells ◽

Cell Activation ◽

Cd4 T Cell ◽

Cell Recovery ◽

Cell Counts ◽

Patients Experience

AbstractIn chronic HIV infection, most untreated patients lose naive CD4+ and CD8+ T cells, whereas a minority preserve them despite persistent high viremia. Although antiretroviral therapy (ART)–mediated viral suppression generally results in a rise of naive and total CD4+ T cells, certain patients experience very little or no T-cell reconstitution. High peripheral T-cell activation has been linked to poor clinical outcomes, interfering with previous evaluations of thymic function in disease progression and therapy-mediated T-cell recovery. To circumvent this, we used the sj/βTREC ratio, a robust index of thymopoiesis that is independent of peripheral T-cell proliferation, to evaluate the thymic contribution to the preservation and restoration of naive CD4+ T cells. We show that the loss of naive and total CD4+ T cells is the result of or is exacerbated by a sustained thymic defect, whereas efficient thymopoiesis supports naive and total CD4+ T-cell maintenance in slow progressor patients. In ART-treated patients, CD4+ T-cell recovery was associated with the normalization of thymopoiesis, whereas the thymic defect persisted in aviremic patients who failed to recover CD4+ T-cell counts. Overall, we demonstrate that efficient thymopoiesis is key in the natural maintenance and in therapy-mediated recovery of naive and total CD4+ T cells.

Download Full-text