Response to immunization with recall and neoantigens after prolonged administration of an HIV-1 protease inhibitor-containing regimen

153

154

Invasive pneumococcal infection is an important cause of morbidity and mortality in HIV-1-infected individuals. B cells play an important role in maintaining serologic memory after infection. IgM memory B cells are significantly reduced in HIV-1-infected patients and their frequency is similar to that observed in other patient groups (splenectomized individuals and patients with primary Ab deficiency) who are also known to have an increased risk of invasive pneumococcal infection. Antiretroviral therapy does not restore marginal zone B cell percentages. Immunization with the 23-valent polysaccharide pneumococcal vaccine shows that HIV-1-infected patients have impaired total IgM and IgG pneumococcal vaccines compared with healthy controls. Loss of switched memory B cells was associated with impaired tetanus toxoid IgG vaccine responses. Results of this study demonstrate that defects in B cell memory subsets are associated with impaired humoral immune responses in HIV-1 patients who are receiving antiretroviral therapy and may be a contributory factor to the increased risk of invasive pneumococcal infection observed in HIV-1 infection.

Section: Loss Of Discretementioning

confidence: 98%

Section: Loss Of Discretementioning

confidence: 99%

Loss of Discrete Memory B Cell Subsets Is Associated with Impaired Immunization Responses in HIV-1 Infection and May Be a Risk Factor for Invasive Pneumococcal Disease

Hart

Steel

Clark

et al. 2007

153

154

“…The full effect of HAART on T cell immunity is still debated. HAART initiation has been associated with the detection of proliferative and Ab responses following immunization with influenza vaccine (16), tetanus toxoid, and inactivated hepatitis A vaccine (17), although these responses are often incomplete (18 -21). We report in this work the consequence of chronic HIV infection on the maintenance of central memory…”

Section: Cells Memory T Cells Have Distinct Phenotypes (Reviewed In mentioning

confidence: 99%

Central Memory CD4+ T Cell Responses in Chronic HIV Infection Are Not Restored by Antiretroviral Therapy

Elrefaei

McElroy

Preas

et al. 2004

A strong CD4+ T cell response has been correlated with better control of HIV infection. However, the effect of HIV on the maintenance of Ag-specific memory CD4+ T cells is not fully understood. We characterized the function and phenotype of memory CD4+ T cells generated by mumps and influenza A or B viruses in HIV-infected individuals receiving highly active antiretroviral therapy (n = 21), HIV-infected long-term nonprogressors (n = 10), and HIV-seronegative volunteers (n = 10). We observed significantly decreased proliferation of the Ag-specific central memory CD4+ T cell population (CD28+/CCR7+/CD45RA−) in the antiretroviral treated HIV-infected individuals compared with the seronegative controls. Restored CD4+ T cell count and decreased HIV viral load while on highly active antiretroviral therapy did not result in increased proliferation, whereas nadir CD4+ T cell count predicted the presence of Ag-specific proliferation. Our results indicate that HIV infection leads to impaired maintenance of virus-induced or vaccine-generated central memory CD4+ T cells that is not restored by HAART.

“…These cells provide an essential resource both for mounting immune responses against novel Ags and also for maintaining T cell homeostasis. In HIV disease, the progressive depletion of naive CD4 ϩ and CD8 ϩ T cells (1) predicts clinical outcome (2) and responsiveness to immunization (3). Compounding the problems associated with the decline in naive T cell numbers, function of the remaining naive CD4 ϩ T cells is impaired in HIV-infected individuals (4).…”

mentioning

confidence: 99%

“…CD31 ϩ naive T cells possess higher levels of TCR excision circles (TRECs) 3 reflective of recent emigration from the thymus (6). Naive CD4 ϩ T cells lacking CD31 expression have proportionally fewer TRECs, presumably a consequence of homeostatic proliferation.…”

mentioning

confidence: 99%

Impaired Induction of CD27 and CD28 Predicts Naive CD4 T Cell Proliferation Defects in HIV Disease

Luciano

Lederman

Valentin-Torres

et al. 2007

Self Cite

Many immunological defects have been described in HIV disease, including a diminished capacity of naive CD4+ T cells to expand after TCR stimulation. The mechanisms underlying impaired naive CD4+ T cell expansion in HIV disease are not well described. Using a rigorous phenotypic definition of naive T cells, we found that cell cycle entry after TCR engagement was restricted to cells that increased surface expression of costimulatory molecules CD27 and CD28. Induction of these receptors, however, was not sufficient to result in cell cycle entry among the CD4+CD31− naive T cell subset. Analyses of cells from HIV-infected persons indicated that naive CD4+CD31+ T cells from these subjects were impaired in their ability to enter the cell cycle after stimulation and this impairment was predicted by the relatively poor induction of costimulatory molecules on these cells. Thus, failure to increase surface expression of costimulatory molecules may contribute to the naive T cell expansion failure that characterizes HIV infection.