Lymphopenia is a simple universal sign of the severity of pathologies like malignancy, somatic diseases, infectious diseases, including COVID 19. It is also a marker for natural tissue mass renewal at pregnancy, postnatal growth, or aging, as well as the toxicity of drugs, irradiation, and other agents that injured health. The dominant interpretation of lymphopenia in terms of immunity is enough for comprehension mentioned topics separately but not united, without contradictions and special reservations for them.
The last of many former controversies is the decrease in cancer death rate per 100,000 population without COVID 19 from 2017 to 2019, followed by a rise in 2020, which is the opposite of the 2017-2020's trend of death' rate from non-malignant somatic diseases among this population [1]. Compromised immunity cannot clarify such opposed trends. They rather point to competition malignant and normal tissues for some factors of the common lymphopoietic source of the host.
The second case, lymphopenia in a large population of cancer patients with Covid is associated with higher mortality [2,3], despite the accompanying specific depletion of Treg lymphocytes [4], which have to liberate anti-cancer immunity according to the dominant view on immune function of this cells' subset.
Several basic features of lymphopoiesis may provide a more suitable field for comprehension of the given examples and like these. These features usually become beyond of attention of immunologists because of concern to unmatured parts of the lymphocytes' pool.
First, the trophic (same as morphogenic/ mitogenic/ angiogenic/ regenerative/ reparative ones) capacity of the circulating unmatured lymphocytes seems more appropriate to solve the two mentioned cases.
Second, lymphopoietic tissues are the most vulnerable of those on which life depends, determining multi-organs syndromes. Organ-specific syndromes (myocardial dysfunction, respiratory symptoms, gastrointestinal symptoms, acute kidney injury, liver cell injury, neurological diseases, dermatological complications) result from the deficit of circulating tissue-committed trophic lymphocytes.
Third, the resource of lymphopoiesis given at the birth, spends during life irreversibly, as fast as renewal/regeneration of tissues demand. Its gradual depletion happens with every act of its natural or artificial tension at an early age with active bone marrow plus thymus, and at an advanced age with rest lymphopoietic function in bone marrow only, changing a regime of cells generation from natural -asymmetric to turbulent- symmetric one. Lymphopenia seems reversible, mainly at the early stage of unidirectional resource’ exhaustion.
In view of this, the mentioned above case one means the increase of morphogenic activity in the whole 2020' population for all tissues independently of their origin (malignant or normal) [5].
The case second confirms the ability of unmatured Treg to participate in the tumor progression by fostering angiogenesis, as it suggested by Zheng X, et al. [6]. Indeed, a human “truly naıve” T cells are able to create the new vessels around artificial scaffolds, too far from the bone marrow and thymus [7,8]. They belongs to recent thymic emigrants with markers CD34, TdT and CD31, which are specific for stem, progenitor and immatured Tcells [9-12]. The reality is the progressive loss of lymphopoiesis’ capacity to generate these naıve Tcells even with natural increasing age, nothing to say of Covid or cancer.
This short analysis may provide context for researchers to design prospective studies based on the dual function and non-homeostatic nature of T-cells lymphopoiesis.
References
- Cornish D, Oven-Williams R (2021) Dataset death rate in England and Wales. People, population and community Births, deaths and marriages.
- Desai A, Mohammed TJ, Duma N, Garassino MC, Hicks LK, et al. (2021) COVID-19 and Cancer. A Review of the Registry-Based Pandemic Response. JAMA Oncology 7: 121882-1890.
- Xiang Q, Feng Z, Diao B, Tu C, Qiao Q, et al. (2021) SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs. Front Immunol 12: 661052. [Crossref]
- Qin C, Zhou L, Hu Z, Zhang S, Yang S, et al. (2020) Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 71: 762-768. [Crossref]
- Shoutko AN (2021) Self- or Not-self is Malignant Tissues for the Host? New Frontiers in Medicine and Medical Research 10: 110-123.
- Zheng X, Jin W, Wang S, Ding H (2021) Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma. Front Immunol 12: 729705.
- Sheehy EJ, Vinardell T, Toner ME, Buckley CT, Kelly DJ (2014) Altering the Architecture of Tissue Engineered Hypertrophic Cartilaginous Grafts Facilitates Vascularisation and Accelerates Mineralisation. PLOS ONE 9: e90716.
- Shoutko AN (2021) The Possible Involvement of Apoptotic Decay of Terminal Deoxynucleotidyl Transferase-Positive Lymphocytes in the Reutilization of the Extracellular DNA Fragments by Surrounding Living Cells. Open Journal of Biophysics 11: 4.
- Larbi A, Fulop T (2014) From "truly naïve" to "exhausted senescent" T cells: when markers predict functionality. Cytometry A 85: 25-35.
- Vi Luan Ha (2019) ASAP3 Is a Focal Adhesion-associated Arf GAP That Functions in Cell Migration and Invasion. Journal of Biological Chemistry 283: 14915-26.
- Le J, Ha VL, Li F, Camacho V, Patel S, et al. (2019) Single Cell Transcriptome Mapping of Human Thymopoiesis Reveals a Continuum of Cell States during T-Lineage Specification and Commitment. blood 134: 1.
- Shoutko AN (2020) Cancer Uses the Common Morphogenesis Source of the Host. Open Journal of Biophysics 10: 4.
