Number Of T-helper Cells Research Articles

Effect of specific chemotherapy on the immune response and resistance to reinfection in experimental schistosomiasis mansoni

Mice infected for 45 days with 120 Schistosoma mansoni cercariae and treated with praziquantel in a dose of 500 mg/kg for two consecutive days had a significant lower resistance to reinfection when challenged two weeks after treatment (45% compared to 88% in infected challenged untreated mice). In praziquantel-treated mice, the reduction in the per cent resistance was accompanied by a diminution in the size of hepatic granulomata and its in vivo correlate the delayed foot pad swelling. Moreover, the granuloma proportionate T-cell subset enumeration revealed a significant reduction in the number of T-helper cells. The humoral immune response as measured by the immediate foot pad swelling was not affected by praziquantel. Results reveal besides the diminution of the state in resistance to reinfection after praziquantel, possible involvement of egg-related pathology as a T-cell mediated reaction and as a mechanical obstacle in maintenance of this resistance.

Immunomodulating Activity of Ginsenoside Rg1 from Panax Ginseng

The immunomodulatory activity of ginsenoside Rg1 from Panax ginseng was studied in mice using sheep red cells as the antigen. It was found that ginsenoside Rg1 at a dose of 10 mg/kg administered for three consecutive days before immunization increased the number of spleen plaque-forming cells, the titers of sera hemagglutinins as well as the number of antigen-reactive T-cells. Ginsenoside Rg1 also increased the number of T-helper cells with respect to the whole T-cell number and the splenocyte natural killer activity. Ginsenoside Rg1 induced an augmentation of the production of IL-1 by macrophages and exerted a direct mitogenic effect on microcultured thymus cells. Ginsenoside Rg1 also partly restored the impaired immune reactivity by cyclophosphamide treatment.

Total Lymphoid Irradiation

Total lymphoid irradiation (TLI) was shown to have potent immunosuppressive effects in patients with Hodgkin's disease. In the last decade a handful of studies assessed the efficacy of TLI in patients with rheumatoid arthritis. A correlation between decline in T-helper cell number and a reduction in disease activity was noted in all studies; however, the toxicity of TLI remains a major problems limiting a more widespread use of this treatment modality.

Regression of oral Kaposi's sarcoma in a case of AIDS on Zidovudine (AZT)

A case with oral Kaposi's sarcoma (KS) is reported that regressed during therapy with Zidovudine (AZT) which was started 5 months after the first dermal and oral tumours were noted. After 6 months of treatment the absolute number of T-helper cells had increased from 54/microliters to 232/microliters and the ratio of T-helper to T-suppressor cells from 0.15 to 0.3. During the same time the lesions of KS on the gingiva, uvula and the body as well as the face disappeared. The lesion of KS on the hard palate regressed.

T‐lymphocyte subsets in recurrent aphthous ulceration

Peripheral T-lymphocyte subsets: T-helper (OKT4) and T-suppressor (OKT8) cells were studied quantitatively in 20 patients with recurrent aphthous ulceration (RAU) in ulcerative, as well as inactive, stages of the disease. The figures were compared with T-lymphocyte subsets from matched control donors with no history of RAU. The ratio of T-helper: T-suppressor cells was significantly lower in both stages in the patients compared with controls due to a significantly increased number of T-suppressor cells in RAU patients. The number of T-helper cells in the patients did not differ significantly in either stage compared with controls. The study support the hypothesis of recurrent aphthous ulceration being a disorder of immunodeficiency.

Ferritin-bearing T-lymphocytes and serum ferritin in patients with breast cancer.

Flow cytometric studies of T-lymphocytes in breast cancer patients show that the number of cells bearing ferritin on their surface is significantly greater than normal. The number of ferritin-bearing T-cells does not appear to be related to the clinical stage of the disease nor to the serum ferritin concentration, though this is higher in cancer patients than in normal women. There is no difference in the number of T-cells positive for interleukin 2 or transferrin receptors nor in the absolute number of T-cells, T-helper cells and B-cells between normal women and those with breast cancer or benign breast disease. However, there is a significant increase in the level of HLA DR-positive T-cells and T-suppressor cells in breast cancer patients. While the significance of ferritin-bearing T-cells is not known an increase in their number appears to be associated with cancer.

FACTORS ASSOCIATED WITH PREVALENT HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION IN THE MULTICENTER AIDS COHORT STUDY

Interviews regarding medical history, life-style, specific drug taking and sexual activities, and physical examinations were administered to 4,955 homosexual men who volunteered for the Multicenter AIDS Cohort Study in Baltimore, Chicago, Los Angeles, and Pittsburgh. Overall, the prevalence of antibodies to human immunodeficiency virus (HIV) in these men was 38.0%. The factor most strongly associated with prevalent HIV infection according to a multiple logistic regression model was rectal trauma, a composite variable which included receptive anal fisting, enemas before sex, reporting of blood around the rectum, and the observation of scarring, fissures or fistulas on rectal examination. Receptive anal intercourse also was strongly associated with HIV infection in the model. The multivariate relative odds for HIV antibody positivity was 7.72 for the highest level of rectal trauma and 3.04 for receptive anal intercourse. Symptoms reported to occur in some persons who subsequently develop acquired immunodeficiency syndrome (AIDS) were frequent among HIV seropositive men (12.9%) but were reported in 8.4% of seronegative men as well. Generalized lymphadenopathy was observed significantly more often in seropositive men (48.8%) compared with seronegative men (11.4%). The prevalence of HIV antibodies was inversely related to the number of T-helper cells and directly related (to a lesser extent) to the number of T-suppressor cells. The results suggest that disruption of the rectal mucosa provides access by HIV to the blood stream and to specific immunologic cells. Since symptoms and generalized lymphadenopathy were often reported among seronegative men, they probably also occur among some seropositive men not currently progressing to AIDS.

Natural history of human immunodeficiency virus infections in hemophiliacs: effects of T-cell subsets, platelet counts, and age.

Serial T-cell subsets and platelet counts were determined in a cohort of 84 hemophiliacs in whom time of seroconversion for human immunodeficiency virus (HIV) antibody could be ascertained. An abrupt decrease in the number of T-helper (T4) cells was seen in 9 patients 12 to 24 months before the acquired immunodeficiency syndrome (AIDS) was diagnosed (p = 0.0007 compared with those who did not develop AIDS). Thrombocytopenia also was associated with an increased risk for AIDS (p = 0.02), as was older age at the time of seroconversion (p = 0.03). Ten patients developed AIDS at 24 to 95 months after seroconversion, for a cumulative incidence (+/- SE) of 18.0% +/- 7.1% at 6 years. Hemophiliacs who had T4 cell counts of less than 200 cells/microL had a 50% +/- 16% cumulative incidence of AIDS within 2 years, indicating that decreasing or very low T4 cell counts have predictive value for the development of AIDS. Furthermore, the data suggest that thrombocytopenia and older age may be markers for a cofactor that increases the risk for AIDS in hemophiliacs.

Antigen responsiveness during tuberculosis: regulatory interactions of T cell subpopulations and adherent cells.

Previous studies from this laboratory demonstrated that adherent mononuclear cells selectively decreased in vitro tuberculin responses in some anergic patients with tuberculosis; subsequently this adherent suppressor cell was characterized as a monocyte. The current study of 41 patients with active pulmonary tuberculosis examined whether T cell subpopulations also acquired antigen-specific suppressor function during Mycobacterium tuberculosis infection, contributed to monocyte-mediated suppression of tuberculin responses, or both. Alteration in the numbers of circulating T-helper (Leu 3a) and T-suppressor (Leu 2a) cells was not observed in patients with tuberculosis, nor did Leu 2a cells selectively modulate in vitro tuberculin responses. The numbers of circulating T gamma cells, a subset of T cells identified by surface receptors for the Fc portion of IgG (Fc gamma R), was increased twofold in patients with active pulmonary tuberculosis. Depletion of T gamma cells from in vitro cell culture consistently and selectively increased tuberculin responsiveness of T cells from patients with tuberculosis. In addition, in the absence of T gamma cells, monocyte-mediated suppression of tuberculin responses was demonstrated in each patient observed. These studies demonstrate that during M. tuberculosis infection T gamma cells acquire antigen-specific suppressor cell activity and suggest that T gamma cells also contribution to immunoregulation modulating the expression of tuberculin-specific suppression by monocytes.

Lymphocyte Subsets in Lung Cancer

Altered cellular immune function has been demonstrated in patients with lung cancer, including decreased numbers of circulating lymphocytes and changes in the percentage of lymphocytes in various functional subsets. We quantitated lymphocyte subsets in 54 patients with lung cancer including patients with limited (stages 1 and 2) nonsmall cell lung cancer (NSCLC, n = 23), advanced (stage 3) NSCLC (n = 16), and small cell cancer (SCLC, n = 15). Serum albumin was decreased in 15 lung cancer patients, and lymphocyte subsets were separately evaluated in these patients. Lymphocyte populations in cancer patients were compared to those of nonsmokers and a smoking patient population. No difference from smokers was noted in patients with limited NSCLC. Patients with SCLC and advanced NSCLC had significantly decreased numbers of T-helper and T-suppressor cells (p less than 0.05). Patients with lung cancer and hypoalbuminemia had the greatest decrease in number of circulating T-helper cells (p less than 0.001). B-lymphocytes were also decreased in patients with advanced NSCLC and patients with hypoalbuminemia (p less than 0.05). A decrease in population of T-lymphocytes subsets is frequent in patients with SCLC, advanced NSCLC, and lung cancer patients with hypoalbuminemia.

ISOLATION OF HIV FROM HEMOPHILIACS

As part of a prospective study of human immunodeficiency virus (HIV) infection in hemophiliacs, peripheral blood mononuclear cells from 72 individuals without AIDS or ARC were cultured for virus. HIV was isolated from 15 out of 66 (23%) of hemophiliacs who were seropositive for HIV, and 0 of 6 seronegative patients. Virus isolation-positive hemophiliacs had significantly (p<.05) reduced T-helper cell numbers, T-helper/T-suppressor ratios, pokeweed mitogen responsiveness and total platelet counts when compared to seropositive hemophiliacs who did not yield HIV upon cultivation. One virus-positive patient has developed AIDS during the study period but no other virus-positive or negative hemophiliac has yet developed ARC or AIDS. Virus isolation-positive hemophiliacs did not differ from virus isolation-negative hemophiliacs in their HIV neutralizing antibody titers. Five of six HIV isolation-positive hemophiliacs were again successfully cultured for virus at later dates ranging from 3-12 months. Nine virus negative individuals remained virus negative when re-cultured at later dates. These data suggest that a significant subgroup of HIV seropositive hemophiliacs persistently harbor live virus and that seropositivity is a valid indication of virus infection. The significant decrease in the number of T-helper cells and the presence of thrombocytopenia in the isolation-positive group may be a reflection of a heavier virus load, and might be an early marker of more significant disease.

TRANSFUSION-ACQUIRED HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION IN NEONATES

Eleven neonates received blood from two HIV infected donors. All developed laboratory and/or clinical evidence of HIV infection, usually in the first year of life. Nine of 11 had serum antibody to HIV when tested between 9 and 16 months of age; two seronegative infants were severely hypogammaglobulinemic when tested. Nine patients developed a variety of illnesses characterized by hepatosplenomegaly, lymphadenopathy, chronic diarrhea, failure to thrive, and thrombocytopenia. Infections, including pneumonia, mucocutaneous candidiasis, and sepsis were a major source of morbidity and mortality. Two children have remained continuously asymptomatic. In follow-up ranging from two to four years, five patients have died, four others had HIV associated illnesses, but recovered and are now healthy. All patients had immunologie abnormalities; the most consistent finding was a decreased proportion of T-helper cells. Three patients had panhypogammaglobulinemia. These infants had significantly lower numbers of T-helper cells compared to patients with normal or increased serum immunoglobulin concentrations (P=0.012). We conclude that exposure to HIV via transfusion in the neonatal period results in an extremely high rate of infection with substantial mortality and morbidity, but clinical recovery occurs in some patients. Second, hypogammaglobulinemia may be more common in infants with HIV infection than previously appreciated.

Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS)

We present a review of the spectrum of human T-lymphotropic virus type III (HTLV-III) infection with particular emphasis on cutaneous manifestations in 217 patients. Correlations are made with immunodeficiency as measured by absolute T-helper cell number. A classification is presented of these dermatologic findings.

Efficacy of acyclovir combined with immunopotentiating agents in the treatment of varicella-zoster

In-vitro and in-vivo evaluation of cellular immune reactions (T-cell subset, E-rosette formation, 2,4-dinitrochlorobenzene, were made in patients with varicella-zoster infection (VZ) and with other intracellular infections. The data demonstrated depressed cellular immunity including a decrease in the number of T-helper cells and a fall in the T-helper/T-suppressor lymphocyte subset ratio to less than 0.7. Three groups of patients with VZ infections were randomly assigned to three regimens: nine patients were given acyclovir alone for five days; ten patients received acyclovir for five days and isoprinosine for ten days; and twelve patients acyclovir for five days and levamisole twice weekly for three weeks. In patients with VZ infections treated with acyclovir and either levamisole or isoprinosine cellular immunity improved faster, while VZ infections in those treated with levamisole healed more rapidly. One patient treated with acyclovir alone had recurrent VZ infection and required a further course of therapy.

Einfluß von Thymostimulin auf die Chemotherapie-induzierte Veränderung der Lymphozytensubpopulationsverteilung

20 patients with primarily inoperable squamous cell carcinoma of the head and neck were treated with 2 cycles of chemotherapy prior to surgical treatment. The lymphocyte subsets were determined prior to chemotherapy, as well as directly after and 3 weeks after start of each chemotherapy cycle. For this, 2 different flow cytometric techniques were used in parallel. After the second cycle of chemotherapy 10 patients were additionally treated with thymostimulin for 2 weeks. The remaining ten patients received no additional immunotherapy and served as control group. Three patients (one in the control group and two in the verum group) had to be excluded from the study because the immunological examination could not be performed in accordance with the protocol. In addition another patient had a local skin reaction so that thymostimulin therapy could not be started as allergy to bovine proteins was suspected. Prior to the first chemotherapy treatment, there is no detectable defect in the distribution of lymphocyte subsets. Under chemotherapy treatment the absolute number of Pan-T cells, T-helper cells, T-suppressor cells and Leu-10 positive B-cells decreased. In contrast, additional treatment with thymostimulin directly after the chemotherapeutic regimen resulted in a marked increase of all T-lymphocytes as well as the Leu-10-positive cells. The results measured with two different flow cytometric techniques were comparable.

Induced differentiation of a transformed clone of Ly-1+ B cells by clonal T cells and antigen.

The present study used cocultures of clonally derived B and T cells, together with an antigen reactive with the membrane Ig of the clonal B cells, to address the issue of B-cell differentiation requirements. The B cells were CH12.LX, an in vitro grown subclone of a murine B-cell lymphoma, which bears surface IgM reactive with sheep erythrocytes. The T cells were alloreactive T-helper-cell hybridomas. Very small numbers of T-helper cells could induce differentiation of cloned B cells without the presence of accessory cells, but such induction was dependent upon the presence of the antigen recognized by the B cell. Induced differentiation of the B cells did not depend on metabolic activity of the T cells, and metabolically active T cells could be replaced by fixed cells or by monoclonal antibody reactive with the class II molecule of the B cell to deliver an Ia-specific differentiative signal. T cells, or alloantibody that reacted with the I-E molecule, induced differentiation of the B cells; those that reacted with the I-A molecule did not. These results define the minimal requirements for major histocompatibility complex-restricted, T-cell-mediated induction of B-cell differentiation.

Long-term seropositivity for human T-lymphotropic virus type III in homosexual men without the acquired immunodeficiency syndrome: development of immunologic and clinical abnormalities. A longitudinal study.

The long-term effects of seropositivity for human T-lymphotropic virus type III (HTLV-III) on T-lymphocyte subsets and health status were evaluated in longitudinal studies of 250 initially healthy homosexual men. The relative risk of having an inverted T-lymphocyte helper-to-suppressor ratio rose from 14.3-fold among short-term seropositive subjects (less than 19 months) to 46.9-fold among long-term seropositive subjects (greater than 29 months) in comparison with the risk among seronegative subjects. Overall, 91.7% of long-term seropositive men had inverted ratios, compared with 12.9% of seronegative men. None of the seropositive men who developed an inverted ratio later reestablished a normal ratio. Both decreased T-helper cell number and percentage (p = 0.003) and increased T-suppressor cell number and percentage (p = 0.03) were significantly correlated with duration of seropositivity. Among seropositive persons, lymphadenopathy was a highly significant short-term as well as long-term consequence, whereas diarrhea, oral thrush, and herpes zoster were correlated with long-term seropositivity. Overall, 50% of long-term seropositive men compared with 16% of seronegative men developed at least one of five clinical symptoms (p less than 0.003). We conclude that a high proportion of persons infected with HTLV-III will develop measurable immunologic and clinical abnormalities.

A functional defect in the early phase of the immune response observed in patients with hemophilia A

In search of a functional immunological defect in patients with hemophilia A, we investigated the early phase of the immune response and found a deficiency in the monocyte-T cell interaction after in vitro exposure to a bacterial antigen. T-cell proliferation in response to Escherichia coli-pulsed autologous monocytes was significantly ( P < 0.025) reduced in hemophiliacs [mean dpm ± SEM ( n = 25): 9036 ± 2600] as compared to healthy controls [mean dpm ± SEM (n = 24): 17,812 ± 2985]. This functional defect was expressed in a severe form (antigen-induced monocyte-T cell interaction ≤2000 dpm) in both HTLV III antibody-positive and -negative patient populations. Significantly decreased T-helper/T-suppressor-cell ratios (mean dpm ± SEM: patients 1.47 ± 0.13; controls 2.04 ± 0.11; P < 0.001)—but without a concomitant reduction in the absolute number of T-helper cells—could also be observed.

HTLV III antibodies and immunological alterations in hemophilia patients.

The clinical, immunological, and serological status of 28 patients with hemophilia A and of 13 patients with hemophilia B was investigated. Thirty-four patients were treated regularly by clotting factor concentrates and 7 patients had been substituted only 1 to 4 times. Almost all patients with severe hemophilia suffered from hepatopathy. No patient had clinical evidence of the acquired immunodeficiency syndrome (AIDS). Asymptomatic hemophiliacs showed a decreased number of T-helper (OKT 4) cells and an increased number of T-suppressor (OKT 8) cells, which resulted in an inversed OKT 4/OKT 8 cell ratio. Natural killer cell activity of all patients was decreased compared to controls. After culture there was no significant difference of NK cell activity between hemophiliacs and controls. This phenomena was interpreted as a possible maturation defect of NK-cells in vivo. No relationship between immunological alterations and hepatopathy, hepatitis markers, CMV antibodies, amount and source of required factor concentrates, and the kind of hemophilia was observed. IgG immunoglobulins were higher and the OKT 4/OKT 8 ratio lower in the eight patients with lymphadenopathy than in patients without lymphadenopathy. The prevalence of antibodies to human T-lymphotropic virus (HTLVIII) was measured in 35 hemophiliacs and in 25 polytransfused patients, most of whom were suffering from acute leukemia. In 8 of 35 hemophiliacs antibodies to HTLVIII virus were detected by an enzyme linked immunosorbent assay (ELISA) and confirmatory tests. All seropositive patients were treated by blood products from the United States. Eight hemophiliacs treated by factor concentrates from German donors only were seronegative. In comparison 2 of 25 examined non-hemophilia patients receiving multiple blood products from local donors were seropositive for HTLVIII. The results show that hemophilia patients treated by imported clotting factor concentrates have a high risk of HTLVIII positivity. Hemophiliacs substituted by blood products obtained by local donor pools have only a small risk of infection. Because non-hemophiliac polytransfused patients had HTLVIII antibodies, there must be asymptomatic virus carriers in the local donor pool. The HTLVIII antibody screening of all donors and the heat treating of factor concentrates will give better therapeutic safety.

EFFECT OF DIETARY NUCLEOTIDES ON LYMPHOCYTE MATURATION: 175

We have shown previously that removal of purines and pyrimidines from the diet (nucleotide free diet-NFD) decreases immune responses both in vivo and in vitro. Allograft rejection and mixed lymphocyte responses and resistance to infectious organisms were all significantly influenced by NFD as compared to chow or NFD with RNA or isolated bases added. NFD affects T-helper cell number and functions as well as suppressor cell activity. In addition, NFD significantly decreases graft-versushost disease mortality in allogeneic bone marrow irradiation chimeras suggesting that NFD impairs the functional T-cell maturation. To determine if this immunologic depression in our various diet fed mice is due to impaired maturation of T-lymphocytes, we assessed lymphoid tissues for the presence of terminal deoxynucleotidyl transferase (TDT). This enzyme is a well characterized marker for immature T-lymphocytes. A statistically higher number of cells positive for TDT activity were found in the thymus and bone marrow of mice on NFD (p<0.02) as compared to cells from animals on chow or NFD with added RNA, uracil, or adenine. These results are consistent with a requirement for either a pyrimidine or purine or both for development of T-helper cell populations. These effects are likely due to a greater dependence of these cells on nucleotide salvage in Gl phase than other lymphocytes. (Supported by Grants 14030 and 35492 from the NCI.)