Lymphocyte Diversity in a 9-Year-Old Boy with Idiopathic CD4+ T Cell Lymphocytopenia

Abstract

Since CD4+ lymphocytopenia can be caused by disturbed thymic T-cell maturation, we investigated the T-cell subsets of a 9-year-old boy fulfilling the diagnostic criteria for CD4+ lymphocytopenia in a follow-up period of 4 years. We found (I) reduced CD45RA expression, (II) enhanced CD45RO expression and (III) a significant increase in γδTCR-bearing T cells. An accelerated apoptosis (11%) was observed in the CD45RO+, but not CD45RA+ subset. These findings provide evidence that a disturbed thymic T-cell maturation process might play a role in the pathogenesis of CD4+ lymphocytopenia.

DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia

“…1,2 ICL is most frequently diagnosed in adults, although pediatric cases have been reported. [2][3][4][5] Patients may show opportunistic infections as a result of a profound deficiency in cellmediated immune responses. 2,6,7 Although the molecular mechanisms underlying this heterogeneous syndrome are still unclear, loss-offunction mutations have been described for genes encoding various regulators of T-cell receptor (TCR) diversity and signaling.…”

“…3,11,12 ICL might result from defective thymic production or output of T cells, exacerbated peripheral consumption, or any combination of these. [4][5][6][12][13][14][15][16][17][18] Cell-intrinsic or cell-extrinsic factors have been identified in ICL that may participate in the perturbation of CD4 1 T-cell homeostasis. These include altered responses to homeostatic cytokines, such as interleukin-2 (IL-2), IL-7, and CXC chemokine ligand 12, 12,15,16 and an enhanced susceptibility of ICL-derived T cells to undergo apoptosis.…”

Non-HIV AIDS presenting with adrenal histoplasmosis and pulmonary tuberculosis: a mesmerising case report and discussion

“…3 In an immunodeficiency syndrome featuring warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM), mutations of the chemokine receptor CXCR4 leading to neutropenia and immunodeficiency were recognized. 4 Other possible mechanisms proposed in the pathogenesis of ICL have been suggested to be in the Fas & Fas ligand, 5 enhanced apoptotic deletion of T-cells, 6 defective thymic maturation of T-cells, 7 reduction in the p56 (Lck) kinase activity, 8 reduced responsiveness of the circulating Tcells to IL-7 (may be due to IL-7 receptor defect), 9 RAG1 & RAG2 gene mutations, 10 a defect in the MAGT 1 (magnesium transporter gene), 11 defective production of TNF-alpha & IFN-gamma, 12 and a heterozygous dominant negative mis-sense mutation of the signalling adaptor protein Uncoordinated 119 (Unc119) that disrupts the association between Lck (lymphocyte specific kinase) and TCR (T-cell receptor). 13 Currently there are no definite treatment options for this novel condition and treatment is generally aimed at preventing infections and malignancies by prophylactic antibiotics and medications as used in a case of HIV infected patient.…”

Multiple Immune Abnormalities in a Patient with Idiopathic CD4+ T-Lymphocytopenia

“…The present patient met the criteria for ICL from age 9. Childhood ICL cases are rare although there have been a few reports (9,10). There is no common feature of childhood ICL, and there is heterogeneity even within childhood cases; two cases showed IgA deficiency with progressive pulmonary infection and another case showed a significant increase in γδTCR-bearing T cells (9,10 (11).…”

“…Childhood ICL cases are rare although there have been a few reports (9,10). There is no common feature of childhood ICL, and there is heterogeneity even within childhood cases; two cases showed IgA deficiency with progressive pulmonary infection and another case showed a significant increase in γδTCR-bearing T cells (9,10 (11). Autoimmunity is also common in ICL, and 9 patients (23.1%) developed autoimmune diseases in the cohort study, either before diagnosis or in the follow-up period (8).…”