Cd8+ Lymphocyte Activation At Human Immunodeficiency Virus Type 1 Seroconversion: Development Of Hla-Dr+ Cd38- Cd8+ Cells Is Associated With Subsequent Stable Cd4+ Cell Levels

Giorgi, Janis V.; Ho, Hong Nerng; Hirji, Karim F.; Chou, Chin Cheng; Hultin, Lance E.; O’Rourke, Sheryl; Park, Lawrence; Margolick, Joseph B.; Ferbas, John; Phair, John P.

doi:10.1093/infdis/170.4.775

Cited by 184 publications

(105 citation statements)

References 23 publications

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“…The opposite was true for resting T cell subsets. The observation that CD8 þ T cells expressing only HLA-DR but not CD38 are lost in Ethiopian AIDS patients is in agreement with a previous prospective study which demonstrated that the presence of this subset is associated with long-term survival and stable CD4 þ T cell counts [14]. Apart from being an activation marker, CD38 is also detected in immature cells [43].The representation of CD4 þ and CD8 þ T cells expressing only CD38 but not HLA-DR is increased in both HIV þ and AIDS groups compared with the HIV ¹ group.…”

Section: Discussionsupporting

confidence: 92%

“…Activated and resting T cell subsets were measured using a combination of HLA-DR and CD38 MoAbs, as described [12,14]. Figure 1c, …”

Section: Activated and Resting T Cell Subsets In Ethiopian Hiv ¹ Himentioning

confidence: 99%

“…Loss of CD4 þ T cells is known to be the hallmark of HIV infection and it is a well accepted laboratory marker of HIV disease progression [6,7]. Also, changes in other T cell subsets have been implicated in HIV þ persons from studies in Europe and North America: expansion of CD8 þ T cells [8], loss of naive CD8 þ T cells, increase of both CD4 þ and CD8 þ T cell memory subsets [9,10] and increased activated CD4 þ and CD8 þ T cell subsets [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts

Messele¹,

Abdulkadir²,

Fontanet³

et al. 1999

Clinical and Experimental Immunology

104

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SUMMARYTo assess possible differences in immune status, proportions and absolute numbers of subsets of CD4 þ and CD8 þ T cells were compared between HIV ¹ healthy Ethiopians (n ¼ 52) and HIV ¹ Dutch (n ¼ 60). Both proportions and absolute numbers of naive CD4 þ and CD8 þ T cells were found to be significantly reduced in HIV ¹ Ethiopians compared with HIV ¹ Dutch subjects. Also, both proportions and absolute numbers of the effector CD8 þ T cell population as well as the CD4 þ CD45RA ¹ CD27 ¹ and CD8 þ CD45RA ¹ CD27 ¹ T cell populations were increased in Ethiopians. Finally, both proportions and absolute numbers of CD4 þ and CD8 þ T cells expressing CD28 were significantly reduced in Ethiopians versus Dutch. In addition, the possible association between the described subsets and HIV status was studied by comparing the above 52 HIV ¹ individuals with 32 HIV þ Ethiopians with CD4 counts > 200/ml and/or no AIDS-defining conditions and 39 HIV þ Ethiopians with CD4 counts < 200/ml or with AIDS-defining conditions. There was a gradual increase of activated CD4 þ and CD8 þ T cells, a decrease of CD8 þ T cells expressing CD28 and a decrease of effector CD8 þ T cells when moving from HIV ¹ to AIDS. Furthermore, a decrease of naive CD8 þ T cells and an increase of memory CD8 þ T cells in AIDS patients were observed. These results suggest a generally and persistently activated immune system in HIV ¹ Ethiopians. The potential consequences of this are discussed, in relation to HIV infection.

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Section: Discussionsupporting

confidence: 92%

“…Activated and resting T cell subsets were measured using a combination of HLA-DR and CD38 MoAbs, as described [12,14]. Figure 1c, …”

Section: Activated and Resting T Cell Subsets In Ethiopian Hiv ¹ Himentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts

Messele¹,

Abdulkadir²,

Fontanet³

et al. 1999

Clinical and Experimental Immunology

104

View full text Add to dashboard Cite

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“…These studies have demonstrated that suppressed viral replication is followed by decreased immune activation, increased expression of co-stimulatory molecules, and increased numbers of naive circulating T cells. 1 ± 9 Other studies indicate that abnormal T cell activation occurs in HIV infection, 42,43,50,51 and that this abnormality increases susceptibility of T cells to become infected, 52 ± 54 or to die by apoptosis. 35,55,56 The abnormal state of activation may therefore be central to the pathogenesis of HIV disease.…”

Section: Immune Reconstitution Following Therapymentioning

confidence: 99%

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection

et al. 1999

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T cells from HIV infected patients undergo spontaneous apoptosis at a faster rate than those from uninfected patients, are abnormally susceptible to activation induced cell death (AICD), and undergo increased apoptosis in response to Fas receptor ligation. These observations have led to the hypothesis CD4 T cell apoptosis may be a mechanism of CD4 T cell depletion and the pathogenesis of AIDS. Successful treatment of HIV infected patients is accompanied by quantitative and qualitative improvements in immune function reflecting at least partial reversibility of the underlying pathogenesis of HIV. In this report we correlate improvements in markers of immune function with a decrease in apoptosis, and changes in its regulation. Therapy with nelfinavir plus saquinavir in combination with two nucleoside analogue inhibitors of reverse transcriptase dramatically reduces plasma viremia and increases CD4 T cell counts. Coincident with these improvements, CD38 and HLA-DR coexpression on both CD4 and CD8 T cells decrease, and CD45RA and CD62L coexpression increase. Furthermore, spontaneous apoptosis decreases in both CD4 and CD8 T cells (CD4 apoptosis 17.4 vs 2.6%, P=0.005; CD8 apoptosis 15.0 vs 1.0%, P50.001), as does both Fas mediated apoptosis (CD4 apoptosis 19.0 vs 3.5%, P=0.03; CD8 apoptosis 13.7 vs 1.5%, P=0.002) and CD3 induced AICD (CD4 apoptosis 13.7 vs 3.2%, P=0.001; CD8 apoptosis 29 vs 2.2%, P=0.08). Changes in apoptosis are not associated with changes in Fas receptor expression, but are significantly correlated with changes in activation marker profiles. Although this suggests a possible regulatory role for the apoptosis inhibitory protein FLIP, direct assessment did not reveal quantitative differences in FLIP expression between apoptosis resistant PBL's from HIV negative patients, and apoptosis sensitive PBL's from HIV positive patients. These findings support the hypothesis that apoptosis mediates HIV induced CD4 T cell depletion, but indicate the need for further studies into the molecular regulation of HIV induced apoptosis.

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“…PD-1 and HLA-DR serve as activation markers of lymphocytes, associated with persistent antigen exposure [24,25] and have been implicated in both activation [26] and exhaustion of CD8 1 T cells in HIV infection [27][28][29]. NK cells in the LNs of HIVindividuals expressed elevated frequencies of HLA-DR (Fig.…”

Section: Nk Cells In Lns Are Highly Activatedmentioning

confidence: 99%

Early viral replication in lymph nodes provides HIV with a means by which to escape NK‐cell‐mediated control

et al. 2011

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Acute HIV infection is marked by dramatic viral replication associated with preferential replication within secondary lymphoid tissues, such as lymph nodes (LNs), that is rapidly but incompletely contained to a viral setpoint. Accumulating evidence supports a role for natural killer (NK) cells in the early control of HIV infection; however, little is known about the location of their antiviral control. Given that HIV replicates profusely in LNs during early infection, we sought to define whether changes occurred in the NK cell infiltrate within these sites during the first year of HIV infection. Surprisingly, NK cell numbers and distribution were unaltered during early HIV infection. LN NK cells expressed decreased inhibitory receptors, were more highly activated, and expressed elevated TRAIL, potentially conferring a superior capacity for NK cells to become activated and control infection. Most noticeably, KIR+ NK cells were rarely detected in the LN during HIV infection, associated with diminished migratory capacity in the setting of reduced expression of CX3CR1 and CXCR1. Thus, incomplete control of HIV viral replication during early disease may be due to the inefficient recruitment of KIR+ NK cells to this vulnerable site, providing HIV a niche where it can replicate unabated by early NK‐cell‐mediated innate pressure.

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Cd8+ Lymphocyte Activation At Human Immunodeficiency Virus Type 1 Seroconversion: Development Of Hla-Dr+ Cd38- Cd8+ Cells Is Associated With Subsequent Stable Cd4+ Cell Levels

Cited by 184 publications

References 23 publications

Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts

Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection

Early viral replication in lymph nodes provides HIV with a means by which to escape NK‐cell‐mediated control

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