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We describe the case of a 14-month-old boy with delayed-onset SCID due to ADA-deficiency which was masqueraded only by failure to thrive. Remarkably, the child had no serious infections and an adequate immune response. However, absolute lymphopenia, eosinophilia and absent thymus on chest x-ray were indicative for immunodeficiency.
CD4(+) T cells expand after transfer into lymphopenic H-2(b) A(beta)-/- mice (I-A(beta)-, I-E(alpha)-deficient mice) but not after transfer into lymphopenic MHC II(Delta/Delta) mice (I-A(alpha)-, I-A(beta)-, I-E(alpha)-, and I-E(beta)-deficient mice), implying that in H-2(b) A(beta)-/- mice, A(alpha) chain and E(beta) chain associate to form a hybrid A(alpha)E(beta) MHC class II molecule. In light of this unexpected result, we reexamined the MHC class II requirement in the survival and lymphopenia-induced proliferation of CD4(+) T cells. Here we show that expansion, but not short-term survival, of CD4(+) T cells depends on interactions with MHC class II molecules in lymphopenic mice. Nevertheless, interactions with classical MHC class II molecules are required for CD4(+) T cells to survive in CD8(+) T-cell-containing mice.
I suggest that the T4 lymphopenia of AIDS may be caused by antibodies raised against the human immunodeficiency virus that block the generation of T4 cells.
A review of 84 patients with cutaneous leishmaniasis treated with sodium stibogluconate (Pentostam) at our institution revealed that three had developed herpes zoster during or shortly after receiving therapy. Because zoster has been associated with depressed cellular immunity, we prospectively followed serial lymphocyte subpopulations in eight patients with cutaneous leishmaniasis who received Pentostam. By day 7 of therapy, the white blood cell count had fallen by a median of 1.15/mm3, the total lymphocyte count by a median of 804/mm3, and the CD4+ lymphocyte count by a median of 306/mm3 (67% of baseline; confidence interval, 52%-78%). An in vitro cell-viability assay demonstrated that Pentostam is not toxic to human mononuclear cells. The administration of Pentostam for the treatment of cutaneous leishmaniasis results in lymphopenia that may be related to the subsequent occurrence of herpes zoster.
The medical records of 17 patients with babesiosis were reviewed. Nine of 17 patients (52.9%) presented with fever (temperature, > 101 degrees F), and 8 of the 9 patients (88.9%) had relative bradycardia. Four of the nine patients (44.4%) had morning temperature spikes during initial hospitalization. As revealed by laboratory analysis, 13 of 17 patients (76.5%) with babesiosis had lymphopenia, and 5 of 17 patients (29.4%) had rouleaux formation in their peripheral blood smears. These newly described clinical and laboratory findings represent additional clinical and laboratory features that may be used as diagnostic clues in the differential diagnosis of babesiosis.
In this methodological study, we describe an assay for analysis of proliferative T cell responses in patients with severe leukopenia. Severe treatment-induced cytopenia is observed in patients with malignant disorders who receive conventional intensive chemotherapy or autologous stem cell transplantation. The quantitative T cell defect can then be characterized by flow cytometric analysis of membrane molecule expression, whereas the functional status of the remaining T cell population is more difficult to evaluate. In the present study, we describe a standardized whole blood assay that requires small sample volumes and can be used for repeated analysis even in severely ill patients. The assay is based on the following strategy: (i) blood samples are diluted with the serum-free medium X-vivo 10, (ii) T cells are activated either with monoclonal immunoglobulin E (IgE) anti-CD3 or anti-CD3 plus anti-CD28; (iii) T cell proliferation is assayed by [(3)H]thymidine incorporation after 4 days of in vitro culture. These proliferative responses are not affected by the plasma levels of interleukin-2 (IL-2), sIL-2-R alpha, IL-7 and IL-15, and the kinetics of the response are not altered by the presence of exogenous cytokines. Detectable proliferation is observed for most patients with treatment-induced cytopenia. We conclude that the assay can be used for functional characterization of remaining T lymphocytes in patients with severe T lymphopenia.
Type I interferons (IFN), including IFN-alpha and IFN-beta, cause severe lymphopenia, resulting from altered lymphocyte recirculation and redistribution. IFN-tau, a product of trophectoderm of ruminant conceptuses and new member of the type I IFN family has not been examined for its effect on leukocyte recirculation. Additionally, differential effects of type I IFNs on the redistribution and recirculation of subsets of T cells have not been reported. The present study determined the effects of IFN-tau on the redistribution and recirculation of ovine leukocytes and T cell subsets. Total peripheral blood leukocytes, lymphocytes, and segmented neutrophils were reduced (p < 0.05) following treatment of lambs with IFN-tau. Furthermore, administration of IFN-tau caused an acute, differential reduction in peripheral blood CD4+ T cells (p < 0.05), CD5+ cells (p < 0.05), and gammadelta TCR+ (p < 0.01) T cells but had no effect on CD8+ T cells (p > 0.05). IFN-tau reduced the percentage of gammadelta T cells by 8-fold and that of CD4+ T cells and CD5+ cells by <2-fold in peripheral blood when compared with control lambs. The reduction in leukocytes, lymphocytes, and neutrophils was observed as early as 6-12 h after administration of IFN-tau, but levels returned to control values within 48 h. These results indicate that IFN-tau, like other members of the type I IFN family, can have immediate effects on leukocyte recirculation and redistribution. The present study is the first to demonstrate that IFN-tau differentially regulates T cell recirculation with the greatest effect on gammadelta TcR+ T cells.
We report the first case of T-cell lymphopenia in a woman with rheumatoid arthritis who developed molluscum contagiosum with infliximab and cyclophosphamide. She presented in July 2000 with optic neuropathy and arthritis refractory to nonsteroidal anti-inflammatory drugs. After starting prednisone and cyclophosphamide, she became leukopenic (1.8x10 cells/microL), a condition that resolved with decreasing of the cyclophosphamide dose. In June 2002, the patient continued to have synovitis despite treatment with prednisone, cyclophosphamide, gabapentin, and celecoxib; blood counts were normal and infliximab was started. Her symptoms improved, but leukocyte counts declined (nadir of 1.5x10 cells/microL) despite discontinuing cyclophosphamide. She developed molluscum contagiosum after 8 months on infliximab (CD4 count, 492; HIV enzyme-linked immunosorbent assay and Western blot negative). Her symptoms flared after 10 months on infliximab; after the dose of infliximab was increased, her CD4 count fell to 114. Infliximab was discontinued and her leukocyte and CD4 count increased. This is the first reported case of leukopenia and T-cell suppression associated with infliximab and cyclophosphamide.
Here we describe a case of unexplained CD4+ T-lymphocyte depletion and cryptococcal meningitis in a patient without evidence of human immunodeficiency virus (HIV) infection. This newly recognized syndrome has been named idiopathic CD4+ lymphopenia (ICL). When HIV infection is suspected in a patient with an opportunistic infection, a CD4+ lymphocyte count should be obtained, even if the patient's HIV test is negative. Patients with persistently low CD4 counts (< 300 cells/microL, or < 20%) who show no evidence of HIV infection, who have no defined immunodeficiency, and who are not receiving therapy associated with CD4 depletion have disease that meets the definition of ICL, and the case should be reported to the Centers for Disease Control.
Lymphopenia induced by treatment for acute lymphoblastic leukaemia is analysed and discussed in relation to the type and incidence of infection occurring in those patients during complete remission. Blood lymphocytes can be placed into three largely independent groups: (1) those lymphocytes susceptible to long-term depletion following irradiation; (2) those lost from the blood during and for a short period after maintenance chemotherapy with methotrexate and 6-mercaptopurine; and (3) the remainder which are not depleted by irradiation or maintenance chemotherapy. The number of cells in each compartment varies from child to child and probably with age but on average is about 1.2 x 10(9)/1. for group 1, 0.7 x 10(9)/1. for group 2 and 0.4 x 10(9)/1. for group 3. Conventional lymphocyte typing crosses these barriers in that: Group 1 consists mainly of E-rosetting cells and cells which show a mitotic response to phytohaemagglutinin; Group 2 also contains E-rosetting cells but contains a major proportion of blood lymphocytes with surface immunoglobulin and essentially all antibody dependent cytotoxic lymphocyte (K-cell) activity; Group 3 comprises E-rosetting cells and a few immunoglobulin-staining cells.
Fas antigen (CD95) is a membrane-associated molecule that mediates apoptotic cell death and may play a role in the induction and maintenance of T cell tolerance. To elucidate the involvement of Fas antigen in human autoimmune diseases, we analysed Fas antigen expression by peripheral T cells from patients with SLE and rheumatoid arthritis (RA), using three-colour flow cytometry. Both CD4+ and CD8+ T cells from SLE patients expressed Fas antigen in a higher density than did these cells from healthy donors and from RA patients. Enhancement of Fas antigen density was noted in Fas+CD45RO+ memory T cells from SLE patients. More remarkably, a significant expression of Fas antigen was observed in CD45RO- naive T cells from SLE patients. CD4+CD45RO- T cells from SLE patients co-expressed Fas antigen and early to intermediate activation antigens such as CD25 and CD71, and late activation antigen HLA-DR in only FashiCD4+ naive T cells. Such up-regulation of Fas antigen expression in SLE patients seems to be clinically meaningful, because mean fluorescence intensity (MFI) of Fas antigen on CD4+ T cell subsets inversely correlates with the absolute size of CD4+ T cell subsets in peripheral blood of SLE patients. These results suggest that T cells with increased Fas antigen expression may be highly susceptible to apoptotic cell death, in vivo. A putative mechanism for lymphopenia in SLE patients is discussed.
The peripheral blood lymphocyte counts of 333 patients with a nasopharyngeal carcinoma and 125 control subjects were compared. The mean pretreatment lymphocyte count in the patients was significantly lower than that of the normal controls (P less than 0.0001). Subgroup analysis of absolute lymphocyte counts in different stages of the disease revealed a stage dependent lymphopenia which became significant when the disease was stage III or over (P less than 0.001). Characterization of peripheral blood lymphocyte subsets in 81 patients and 46 normal control subjects revealed a significant reduction of the absolute Pan T (T11) lymphocytes in the patients (P less than 0.0001). Both the absolute numbers of T helper (T4) and suppressor cells (T8) were reduced in the patients (P less than 0.0001 and less than 0.026, respectively). While the percentage of T4 was reduced (P less than 0.0001), the percentage of T8 was elevated (P less than 0.02), resulting in a reduced T4/T8 ratio (P less than 0.0001). The mean absolute and percentage counts of T11, T8 and B did not correlate with different stages of the disease.
Bacteraemia often carries a poor prognosis despite prompt antibiotic therapy and is associated with late morbidity and mortality that is difficult to explain. Here, we describe perisistent B- and T- cell lymphopenia in a cohort of patients with Gram-positive and Gram-negative bacteraemia. This suggests previously unrecognized mechanisms of subversion of immunity by pathogens and might explain the comorbidity of blood stream infection with bacteria.
We report a 6-year-old girl in whom Mycoplasma pneumoniae infection presenting with erythema multiforme, multiorgan, and hematologic dysfunctions induced a long-standing, marked B-cell lymphopenia. An increase of CD8+ lymphocytes was also detected. We suggest that a selective cytotoxic T lymphocyte-dependent B cell lysis and the expansion of super-antigen activated CD8+ T cells may account for the multiorgan and hematologic disturbances triggered by M. pneumoniae.
Congenic BioBreeding (BB) rats, homozygous for the autosomal lymphopenia (Lyp) gene (Lyp/Lyp), heterozygous (Lyp/+), or wild-type (+/+), were immunized with the T cell-dependent bacteriophage PhiX174 to determine effects of Lyp on primary and secondary antibody responses. The primary PhiX174 antibody response did not differ between the three different genotypes. In contrast, the secondary immune response, expressed as the peak neutralizing titer, was markedly reduced in Lyp/Lyp (9.9+/-3.2; mean value+/-S.E.M. for seven rats) compared to both Lyp/+ (51+/-12; n=13; P=0.006) and +/+ (100+/-20; n=7; P=0.004) BB rats. We suggest that the secondary antibody response to the T cell-dependent neoantigen PhiX174 is linked in a recessive manner to genetic factor(s) in the Lyp gene region.
Plasma cortisol levels were determined in 51 children on admission to hospital for a variety of acute illnesses which were associated with a lymphopenia, and again when the lymphocyte count had returned to normal. The ratio cortisol level/lymphocyte count was much higher in the acute phase of the illness than later when the lymphocyte count had returned to normal. It is concluded that the lymphocyte count is a useful means of detecting an acute stress condition, and the time of return of normal plasma cortisol levels.
The clinical outcome of 42 acutely unwell infants <3 months old with lymphopenia was retrospectively compared with that of 42 controls. Lymphopenic infants were significantly more likely to require active resuscitation and intensive care, independent of total leucocyte count, gender, degree of prematurity, and diagnosis.
A subgroup of thymoma patients is affected by severe immunodeficiency clinically resembling an HIV infection (Good syndrome). These individuals are characterized by B lymphopenia with B-lymphopoiesis deficiency. To investigate the pathogenesis of this unique condition, we studied the T-cell repertoire in blood and bone marrow samples by heterogeneity length analysis of CDR3 beta variable regions of the T-cell receptor (spectratyping). While no alterations were found in the peripheral blood, we detected an oligoclonal population of beta variable 8 (BV8) CD8(+) T cells in 5 of 5 bone marrow samples. No lymphocyte expansions were found in the bone marrow of 2 thymoma patients with normal B-cell counts, 2 healthy donors, and 3 patients with diseases unrelated to thymoma. These data suggest that an immune response toward an unknown antigen is taking place in the bone marrow of B-lymphopenic thymoma patients. We propose that BV8 CD8(+) T cells may play a role in the pathogenesis of this immunodeficiency syndrome.