scholarly journals Changes in T-helper cell function in human immunodeficiency virus- infected children during didanosine therapy as a measure of antiretroviral activity

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2196-2202
Author(s):  
M Clerici ◽  
E Roilides ◽  
KM Butler ◽  
L DePalma ◽  
D Venzon ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Bacterial Infections ◽  
Cell Function ◽  
Interleukin 2 ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Asymptomatic Patients ◽  
Immunodeficiency Virus ◽  
P24 Antigen

Didanosine has shown activity against the human immunodeficiency virus (HIV) in both children and adults. We prospectively assessed T-helper cell (Th) function as determined by in vitro interleukin-2 (IL-2) production in response to a panel of T-cell stimuli in 22 HIV-infected children before and during didanosine therapy and we correlated the incidence of opportunistic and recurrent bacterial infections with changes in p24 antigen and CD4 counts. Didanosine (270, 360, or 540 mg/m2/d) was administered orally for periods ranging from 8 to 40 weeks (mean, 24 weeks). Five of six asymptomatic patients (Centers for Disease Control P-1) compared with 6 of 16 symptomatic (P-2) patients exhibited improved Th function (greater than threefold increase in IL-2 production to at least 2 of the 4 stimuli) during therapy. Of 12 patients without infections during therapy, 9 (75%) showed improvement in Th function, compared with only 2 of 10 patients with infections (P = .03). Notably, the incidence of infections was not correlated with improvements in CD4 count or decreases in p24 antigen. Improvement in Th function during didanosine therapy is correlated with decreased incidence of infections. Assessment of Th function may provide an additional measurement of immunologic response to antiretroviral therapy.

scholarly journals Changes in T-helper cell function in human immunodeficiency virus- infected children during didanosine therapy as a measure of antiretroviral activity

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2196-2202 ◽  
Author(s):  
M Clerici ◽  
E Roilides ◽  
KM Butler ◽  
L DePalma ◽  
D Venzon ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Bacterial Infections ◽  
Cell Function ◽  
Interleukin 2 ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Asymptomatic Patients ◽  
Immunodeficiency Virus ◽  
P24 Antigen

Abstract Didanosine has shown activity against the human immunodeficiency virus (HIV) in both children and adults. We prospectively assessed T-helper cell (Th) function as determined by in vitro interleukin-2 (IL-2) production in response to a panel of T-cell stimuli in 22 HIV-infected children before and during didanosine therapy and we correlated the incidence of opportunistic and recurrent bacterial infections with changes in p24 antigen and CD4 counts. Didanosine (270, 360, or 540 mg/m2/d) was administered orally for periods ranging from 8 to 40 weeks (mean, 24 weeks). Five of six asymptomatic patients (Centers for Disease Control P-1) compared with 6 of 16 symptomatic (P-2) patients exhibited improved Th function (greater than threefold increase in IL-2 production to at least 2 of the 4 stimuli) during therapy. Of 12 patients without infections during therapy, 9 (75%) showed improvement in Th function, compared with only 2 of 10 patients with infections (P = .03). Notably, the incidence of infections was not correlated with improvements in CD4 count or decreases in p24 antigen. Improvement in Th function during didanosine therapy is correlated with decreased incidence of infections. Assessment of Th function may provide an additional measurement of immunologic response to antiretroviral therapy.

Reconstitution of Long-Term T Helper Cell Function after Zidovudine Therapy in Human Immunodeficiency Virus-Infected Patients

1992 ◽  
Vol 166 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Mario Clerici ◽  
Alan L. Landay ◽  
Harold A. Kessler ◽  
John P. Phair ◽  
David J. Venzon ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Function ◽  
T Helper Cell ◽  
Zidovudine Therapy ◽  
Helper Cell ◽  
T Helper ◽  
Immunodeficiency Virus

Defective T-helper cell function after T-cell–depleting therapy affecting naive and memory populations

Blood ◽  
2002 ◽  
Vol 99 (11) ◽  
pp. 4053-4062 ◽  
Author(s):  
Andreas Heitger ◽  
Patricia Winklehner ◽  
Petra Obexer ◽  
Johannes Eder ◽  
Claudia Zelle-Rieser ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Interleukin 2 ◽  
T Helper Cell ◽  
Helper Cell ◽  
High Dose ◽  
T Helper

Impaired T-cell function after T-cell– depleting (TCD) therapy has been hypothesized to be related to a transient predominance of extrathymically expanding memory T cells. To test whether after TCD therapy the naive T-helper cell population is functionally intact, the in vitro immune response of CD4+CD45RA+ (naive) and of CD4+CD45RA− (memory) cells to polyclonal mitogens (immobilized anti-CD3, phytohemagglutinin) was analyzed by flow cytometry in 22 pediatric patients after high-dose chemotherapy (including 5 after autologous and 5 after allogeneic stem cell support). At 1 to 3 months after TCD therapy, patient samples showing decreased lymphoproliferative responses also showed a reduced induction of the early activation marker CD69 by CD4+ T cells from 4 to 72 hours after stimulation even when supplemented with exogenous interleukin-2. This defect affected CD4+CD45RA− cells, but, strikingly, also CD4+CD45RA+ cells, including samples in which CD4+CD45RA+ cells were more than 90/μL, thus indicating ongoing thymopoiesis. Histogram analyses showed the median peak channel of CD69 in control CD4+CD45RA+cells rising 98-fold (median) but only 28-fold in patient cells (P < .0001). Apoptosis as detected by annexin V staining was increased in resting patient CD4+ T cells (25% versus 6%) and also affected CD4+CD45RA+ cells (12% versus 5%, P < .01). When peripheral blood mononuclear cells (PBMCs) were enriched for T cells, stimulatory responses of CD4+ cells and of CD4+CD45RA+ cells markedly improved. Thus, after TCD therapy suppressor factors contained in the non–T-cell fraction of PBMCs may affect T-helper cells irrespective of their naive or memory phenotype thus extending T-cell dysfunction to the presumably thymus-dependently regenerated T cells.

T helper cell epitopes of the human immunodeficiency virus (HIV-1) nef protein in rats and chimpanzees

1992 ◽  
Vol 29 (4) ◽  
pp. 489-499 ◽  
Author(s):  
Jerome Estaquier ◽  
Christophe Boutillon ◽  
Jean-Claude Ameisen ◽  
Helene Gras-Masse ◽  
Jean-Pierre Lecocq ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Limited Breadth of a T-Helper Cell Response to a Human Immunodeficiency Virus Envelope Protein

2003 ◽  
Vol 77 (7) ◽  
pp. 4231-4236 ◽  
Author(s):  
X. Zhan ◽  
K. S. Slobod ◽  
S. Surman ◽  
S. A. Brown ◽  
T. D. Lockey ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Response ◽  
Envelope Protein ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Virus Envelope ◽  
Immunodeficiency Virus ◽  
Natural Variant ◽  
Virus Envelope Protein

ABSTRACT Single-envelope human immunodeficiency virus (HIV) vaccines have been studied for more than a decade, with some successes in homologous challenge experiments in nonhuman primates but with no clear successes in clinical trials. To gain insight into the breadth of the immunity elicited by such vaccines, we have dissected the T-helper cell response of C57BL/6 mice to an individual, molecularly cloned envelope protein. Here, we report that T-helper cells responsive to HIV type 1 1035 envelope are very highly restricted in C57BL/6 animals: seven different hybridomas recovered from five separate mice recognized the same peptide, PKVSFEPIPIHYCAP, located in the C2 region of gp120. Three of these hybridomas were tested on a natural variant of the peptide but failed to respond. A more extensive analysis of whole splenic populations from other C57BL/6 mice immunized with the 1035 envelope reproducibly confirmed that the gp120-specific T-helper response was almost exclusively focused on a single epitope. We conclude that single-envelope vaccines may frequently fail to provoke an immune response sufficiently diverse to recognize variant sequences among circulating HIV. The results encourage the inclusion of more than one envelope in future vaccines to enhance the potential diversity and respective surveillance capacities of responding T-helper cell populations.

scholarly journals Lack of enhanced T-helper cell function in uremic patients with circulating alloreactive antibodies.

1995 ◽  
Vol 5 (7) ◽  
pp. 1441-1450
Author(s):  
A Shoker ◽  
R Miller ◽  
R Uldall ◽  
E Friedman ◽  
S Angra ◽  
...  
Keyword(s):  
T Helper Cells ◽  
Blood Lymphocyte ◽  
Cell Function ◽  
Interleukin 2 ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Cd4 Cells ◽  
Helper Cells ◽  
Uremic Patients

Some uremic patients with a history of blood transfusion, pregnancy, and previous transplantation maintain high levels of alloreactive cytotoxic antibodies in the absence of continuous exogenous allogenic stimuli and are thus considered sensitized to the major histocompatibility proteins. To differentiate into antibody-producing cells, B lymphocytes must interact with T-helper (CD4+) cells. Whether ongoing help from these cells is necessary for the B cells to continue producing cytotoxic alloreactive antibodies in these sensitized uremic patients is unknown. To gain insight into the cellular mechanisms that are associated with sustained alloantibody production, T cell activation markers were measured and specific and nonspecific T-helper cell function was studied in three uremic groups with different levels of panel reactive antibodies: 10 patients whose sera reacted to more than 80% of a panel of normal lymphocytes for at least 6 months before the study were highly sensitized, 20 patients whose sera reacted to less than 80% of the panel were moderately sensitized, and 10 nonsensitized patients whose sera did not react to any cell on the panel. The number of total and activated T-helper cells was similar in the highly sensitized and nonsensitized patients. Peripheral blood lymphocyte proliferation in response to plant lectins, soluble OKT3, or alloantigens was similar in the three uremic groups. The spontaneous proliferation of pure T-helper cells and proliferative responses to immobilized OKT3 or alloantigens were also similar in highly sensitized and nonsensitized patients. Alloreactive interleukin-2-producing cell frequencies with pure CD4+ cells as responding cells were 771 +/- 77.9/10(6) cells in highly sensitized, 945 +/- 252/10(6) cells in nonsensitized, and 973 +/- 114/10(6) cells in controls (P = not significant). Panel reactive antibody levels did not correlate with any of the measures of T helper responses. There was a significant decrease of peripheral blood lymphocyte responses to alloantigens and anti-CD3 antibody in all uremic patients as compared with normals, suggesting a dysfunction in accessory cells that was quantitatively similar in sensitized and nonsensitized patients. In spite of the continuous production of alloantibodies by B cells, there is no evidence of either specific or nonspecific enhancement of T-helper cell function in sensitized patients. The absence of T cell immunity to alloantigens suggests that sustained activation of T-helper cells with subsequent interleukin-2 production is not necessary to maintain alloreactive B cell function.

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