Human Immunodeficiency Virus Infection in the US Air Force: Seroconversions, Clinical Staging, and Assessment of a T Helper Cell Functional Assay to Predict Change in CD4+ T Cell Counts

Lucey, Daniel R.; Melcher, Gregory P.; Hendrix, Craig W.; Zajac, Robert A.; Goetz, David W.; Butzin, Clifford A.; Clerici, Mario; Warner, R.G.; Abbadessa, Steven; Hall, Kevin D.; Jaso, Rene; Woolford, Brian; Miller, S D; Stocks, Naomi I.; Salinas, Cynthia M.; Wolfe, William H.; Shearer, Gene M.; Boswell, R N

doi:10.1093/infdis/164.4.631

Cited by 82 publications

(20 citation statements)

References 40 publications

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“…Marked defects in CD4 + lymphocyte function precede the decline in peripheral CD4 + lymphocyte number. An early marker of this immune defect is the inability to respond to recall antigens in vivo and in vitro [36].…”

Section: Discussionmentioning

confidence: 99%

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

Peruzzi

Azzari

Galli

et al. 2002

Clinical and Experimental Immunology

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SUMMARY To analyse the effect of highly active antiretroviral therapy (HAART) on T-lymphocyte functions we selected seven HIV-1 perinatally infected children (CDC immunological category 1 or 2) who had neither a fall in their plasma HIV-1 RNA levels nor a significant rise in CD4+ lymphocyte counts while receiving HAART. Clinical signs and symptoms were monitored monthly. Plasma viral load, CD4+, CD8+, CD19+ lymphocyte counts and in vitro T-lymphocyte proliferative responses to mitogens (anti-CD3, phytohaemoagglutinin, concanavalin A and pokeweed mitogen) and recall antigens (Candida albicans and tetanus toxoid) were tested at baseline and after 1, 3, 6 and 12 months of HAART. Twenty-two healthy age-matched children were studied as controls. A gain in body weight, no worsening of the disease and no recurrence of opportunistic infections were observed. At baseline, the majority of the children had low responses to mitogens, and all of them had a defective in vitro antigen-specific T-lymphocyte response (<2 standard deviations below the mean result for controls). During HAART, a significant increase in the response to mitogens and antigens was observed in all the patients. The T-lymphocyte response was restored more consistently against antigens to which the immune system is constantly exposed (Candida albicans, baseline versus 12 months: P < 0·001) compared with a low-exposure antigen (tetanus toxoid, baseline versus 12 months: P < 0·01). HAART restores in vitro T-lymphocyte responses even in the absence of a significant viral load decrease and despite any significant increase in CD4+ lymphocyte counts. It implies that a direct mechanism might be involved in the overall immune recovery under HAART.

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Section: Discussionmentioning

confidence: 99%

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

Peruzzi

Azzari

Galli

et al. 2002

Clinical and Experimental Immunology

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“…In addition to a decrease in the number of CD4 ϩ T cells, functional defects in cell-mediated immunity play an important role in the pathogenesis of immunodeficiency associated with HIV-1 infection (11,12). The clinical relevance of CD154 as well as its central role as a regulator of cell-mediated and humoral immunity led to studies that examined whether induction of CD154 is defective in CD4 ϩ T cells from HIV-1 ϩ patients.…”

Section: T He Interaction Between T Cells and Apcs Is An Event Centramentioning

confidence: 99%

Role of CD40-Dependent Down-Regulation of CD154 in Impaired Induction of CD154 in CD4+ T Cells from HIV-1-Infected Patients

Subauste

Wessendarp

2007

The Journal of Immunology

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CD40-CD154 interaction is pivotal for cell-mediated immunity. There are contradictory reports on whether HIV-1 infection impairs CD154 induction. The interaction between CD40 and CD154 is important not only because it results in activation of APCs but also because it controls CD154 by diminishing expression of this molecule. Compared with healthy controls, CD4+ T cells from HIV-1+ patients had impaired induction of CD154 when T cell activation was mediated by CD40+ APCs. In contrast, T cell activation in the absence of these cells resulted in normal CD154 expression. CD154 induction in HIV-1+ patients and controls were similar upon blockade of CD40-CD154 binding. Defective regulation of CD154 appeared to occur downstream of the control of mRNA levels because up-regulation of CD154 mRNA was not impaired by HIV-1 infection. This work identifies CD40 as a mediator of impaired CD154 induction in HIV-1 infection and explains why this defect was not detected by studies where T cell activation was triggered independently of CD40+ APCs. In addition, dysregulation of CD154 in HIV-1 infection likely contributes to immunodeficiency because diminished expression of CD154 induced by CD40 is of functional relevance, resulting in decreased dendritic cell maturation.

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“…It (11). These stimuli were also selected for study in young children because we have previously reported that: (a) PBL from both adult (10) and pediatric (12) HIV + individuals exhibit a spectrum of Th defects to this panel of T cell stimuli that is predictive for AIDS progression in adults (10,13) and for susceptibility to opportunistic and bacterial infections in children (12); and (b) different patterns of function of the Th pathways are predictive for human solid organ allograft rejection ( 14). The results of this study will be relevant for assessing Th and antigen presenting cell functions that are required for immunologic maturation in infants, and may be important for vaccination and modulation of immunity in infants and children.…”

Section: Introductionmentioning

confidence: 99%

Analysis of T helper and antigen-presenting cell functions in cord blood and peripheral blood leukocytes from healthy children of different ages.

et al. 1993

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The development of antigen-specific functional T lymphocyte immunity in infants and children is an area of immunology that needs elucidation. Leukocytes from cord blood (CBL) and from PBL of children of different ages who were in the hospital for minor surgical procedures were compared with PBL from healthy adults for their ability to generate T helper cell (Th) responses assessed by in vitro proliferation and IL-2 production after stimulation with: influenza A virus (FLU); tetanus toxoid (TET); adult allogeneic PBL that were either undepleted (ALLO) or depleted ofadherent antigen presenting cells (ALLONW); and PHA. CBL generated Th responses to AL-LONW, ALLO, and PHA, but not to FLU or TET. PBL from infants between 6 and 13 mo of age responded to ALLO and PHA; none responded to FLU or ALLONW, and two of four responded weakly to TET. PBL from children between 13 and 26 mo ofage responded to all stimuli except FLU, to which only one child responded marginally. PBL from children older than 36 mo responded to all stimuli at levels comparable to those of PBL from adults.The use of undepleted and adherent cell-depleted CBL and PBL from children of different ages as allogeneic stimulators of responses generated by PBL from adults indicated that the antigen presenting function of CBL and PBL from children 13 mo or older are sufficiently developed to present alloantigen, whereas PBL from children younger than 13 mo are not. Therefore, our results indicate that age-dependent differences exist in both T helper and antigen-presenting functions of CBL and PBL from children of different ages. Surprisingly, CBL appear to be more efficient in antigen-presenting function than PBL from children younger than 13 mo. These findings are important for establishing developmental parameters of T helper cell immunity relevant for pediatric infection and transplantation in infants and children. (J. Clin. Invest. 1993. 91:2829-2836

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Human Immunodeficiency Virus Infection in the US Air Force: Seroconversions, Clinical Staging, and Assessment of a T Helper Cell Functional Assay to Predict Change in CD4+ T Cell Counts

Cited by 82 publications

References 40 publications

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

Role of CD40-Dependent Down-Regulation of CD154 in Impaired Induction of CD154 in CD4+ T Cells from HIV-1-Infected Patients

Analysis of T helper and antigen-presenting cell functions in cord blood and peripheral blood leukocytes from healthy children of different ages.

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