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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decreased CD4(+) T cell counts are the best marker of disease progression during HIV infection. However, CD4(+) T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4(+) T cell subsets influences disease severity. CD4(+) T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127(+)CD25(low/-) subset includes IL-2-producing naive and central memory T cells; the CD127(-)CD25(-) subset includes mainly effector T cells expressing perforin and IFN-gamma; and the CD127(low)CD25(high) subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4(+)CD127(-)CD25(-) T cells that is related to an absolute decline of CD4(+)CD127(+)CD25(low/-) T cells. Interestingly, this expansion of CD4(+)CD127(-) T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4(+)CD127(-)CD25(-) T cells correlated directly with the levels of total CD4(+) T cell depletion and immune activation. CD4(+)CD127(-)CD25(-) T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4(+) T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4(+) T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4(+) T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals.
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PMID:CD127 and CD25 expression defines CD4+ T cell subsets that are differentially depleted during HIV infection. 1839 Jul 43

Co-infection with HCV and HIV-1 is a problem of increasing importance and the role of innate cellular immunity in this co-infection is incompletely understood. Here, we have observed sharply elevated numbers of CD56(-)CD16(+) perforin(low) NK cells in HCV/HIV-1 co-infected subjects on antiretroviral therapy. Interestingly, this expansion of unconventional CD56(-) NK cells rapidly reverted when HCV was suppressed by IFNalpha and ribavirin treatment, and was not seen in mono-infected control groups. In vitro experiments suggested that this effect of treatment was due to suppression of HCV viremia rather than a direct effect of IFNalpha on these cells. In contrast, the conventional CD56(+) NK cells were largely unchanged in subjects with high HCV loads, although they exhibited slightly decreased perforin expression. With delayed kinetics, the CD56(bright) immuno-regulatory NK cell subset temporarily increased to supranormal levels in response to HCV treatment. In contrast to the NK compartment, the CD1d-restricted NKT cells were severely reduced by the co-infection and not restored by treatment. Together, our data suggest that the high HCV loads in HCV/HIV-1 co-infection alter the NK cell compartment in a way not observed in HCV mono-infection.
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PMID:Expansion of CD56- NK cells in chronic HCV/HIV-1 co-infection: reversion by antiviral treatment with pegylated IFNalpha and ribavirin. 1849 40

HIV vaccine research increasingly uses polychromatic flow cytometry as a tool to monitor T cell responses. The use of this technology allows for the analysis of highly defined subsets of cells with unique phenotypes and functions. Ultimately, such studies may identify surrogate markers of protection from disease progression. However, this powerful technology comes with a number of technical hurdles, and there is a need to standardize the assays and protocols used in clinical trial monitoring. Here an optimized protocol, with variations for specific circumstances, is presented. This protocol covers the analysis of multiple cytokines, cell surface markers, and other functional markers such as perforin, CD107, and CD154. While the protocol can be adapted to various numbers of fluorescence parameters, optimized panels of 8-10 colors are presented.
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PMID:Multiparameter flow cytometry monitoring of T cell responses. 1902 Aug 38

Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin(-) GrmB(-) GrmA(+/-) GrmK(+); in CMV-specific cells, it was perforin(+) GrmB(+) GrmA(+) GrmK(-/+); and in EBV- and HIV-1-specific cells, it was perforin(-/+) GrmB(+) GrmA(+) GrmK(+). On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK(+) profile was associated with early-stage memory CD8 T-cell differentiation, the perforin(+) GrmB(+) GrmA(+) profile with advanced-stage differentiation, and the GrmB(+) GrmA(+) Grmk(+) profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure.
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PMID:Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with function, differentiation stage, and antigen exposure. 1917 26

We evaluated NK cell subsets and functions in previously immunodeficient HIV patients responding to ART. Cytokine receptor mRNA was quantitated in purified CD56+ cells. Data were correlated with CD4+ T-cell counts and IFNgamma responses to CMV. NK cell IFNgamma responses to K562 cells and proportions of CD56lo NK cells were correlated in patients (p < 0.001) and both were lower than in controls (p < 0.001 and p = 0.008, respectively), so all patients had poor NK cell function. Proportions of CD56hi NK cells correlated inversely with current CD4+ T-cell counts (p = 0.006) and perforin expression in CD56hi NK cells was higher in patients than controls (p < 0.05). Hence increased proportions and cytolytic function of CD56hi NK cells may partially compensate for CD4+ T-cell deficiency. NK cell IFNgamma responses correlated inversely with expression of IL-10 and IL-12 receptor mRNA. Expression of these transcripts is reduced by exposure to the cytokines, which may reflect immune activation in immunodeficient patients.
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PMID:Could natural killer cells compensate for impaired CD4+ T-cell responses to CMV in HIV patients responding to antiretroviral therapy? 1940 37

CD4 T lymphocytes expressing CD8dim (DP: CD4 CD8dim) or NKG2D represent cytotoxic effector populations, which have been involved in viral infections and chronic diseases. The frequency of DP cells was analyzed by flow cytometry in 300 consecutive HIV-infected patients and 50 healthy controls. NKG2D expression and memory/effector markers in CD4 T cells were also studied, in addition to virologic and genetic factors involved in DP T-cell expansion. HIV-infected patients showed a significantly higher frequency of DP cells than controls, mainly in patients with advanced disease. Expansion of DP cells was related to NKG2D appearance in CD4 T cells and was predicted by CD4 CD28null T-cell levels. Cells expressing CD8dim and NKG2D cells are closely related populations with a similar pattern of surface markers, perforin expression, and responses to activation. We also found that these subsets seem to share an ontogenic relationship and TcR oligoclonality. In this way, cytomegalovirus infection and certain HLA alleles, such as DR7, conditioned the expansion of DP cells. Their common ontogenic origin and oligoclonality, possibly due to repeated encounters with the same antigen, could result in a limitation of the repertoire of responder cells and in a worse prognosis of HIV infection.
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PMID:CD8dim and NKG2D expression defines related subsets of CD4+ T cells in HIV-infected patients with worse prognostic factors. 1946 24

Mycobacterium bovis BCG is an attractive vaccine vector against breast milk HIV transmission because it elicits Th1-type responses in newborns. However, BCG causes disease in HIV-infected infants. Genetically attenuated Mycobacterium tuberculosis (Mtb) mutants represent a safer alternative for immunocompromised populations. In the current study, we compared the immunogenicity in mice of three different recombinant attenuated Mtb strains expressing an HIV envelope (Env) antigen construct. Two of these strains (DeltalysA DeltapanCD Mtb and DeltaRD1 DeltapanCD Mtb) failed to induce significant levels of HIV Env-specific CD8(+) T cell responses. In striking contrast, an HIV-1 Env-expressing attenuated DeltalysA Mtb containing a deletion in secA2, which encodes a virulence-related secretion system involved in evading adaptive immunity, generated consistently measurable Env-specific CD8(+) T cell responses that were significantly greater than those observed after immunization with BCG expressing HIV Env. Similarly, another strain of DeltalysA DeltasecA2 Mtb expressing SIV Gag induced Gag- and Mtb-specific CD8(+) T cells producing perforin or IFNgamma, and Gag-specific CD4(+) T cells producing IFNgamma within 3 weeks after immunization in adult mice; in addition, IFNgamma-producing Gag-specific CD8(+) T cells and Mtb-specific CD4(+) T cells were observed in neonatal mice within 1 week of immunization. We conclude that DeltalysA DeltasecA2 Mtb is a promising vaccine platform to construct a safe combination HIV-TB vaccine for use in neonates.
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PMID:Recombinant pro-apoptotic Mycobacterium tuberculosis generates CD8+ T cell responses against human immunodeficiency virus type 1 Env and M. tuberculosis in neonatal mice. 2003 29

CMV infection is characterized by high of frequencies of CD27-CD28- T cells. Here we demonstrate that CMV-specific CD4+CD27-CD28- cells are regulatory T cells (TR). CD4+CD27-CD28- cells sorted from CMV-stimulated PBMC of CMV-seropositive donors inhibited de novo CMV-specific proliferation of autologous PBMC in a dose-dependent fashion. Compared with the entire CMV-stimulated CD4+ T-cell population, higher proportions of CD4+CD27-CD28- TR expressed FoxP3, TGFbeta, granzyme B, perforin, GITR and PD-1, lower proportions expressed CD127 and PD1-L and similar proportions expressed CD25, CTLA4, Fas-L and GITR-L. CMV-CD4+CD27-CD28- TR expanded in response to IL-2, but not to CMV antigenic restimulation. The anti-proliferative effect of CMV-CD4+CD27-CD28- TR significantly decreased after granzyme B or TGFbeta inhibition. The CMV-CD4+CD27-CD28- TR of HIV-infected and uninfected donors had similar phenotypes and anti-proliferative potency, but HIV-infected individuals had higher proportions of CMV-CD4+CD27-CD28- TR. The CMV-CD4+CD27-CD28- TR may contribute to the downregulation of CMV-specific and nonspecific immune responses of CMV-infected individuals.
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PMID:Regulatory function of cytomegalovirus-specific CD4+CD27-CD28- T cells. 2003 45

FOXP3(+)CD8(+) T cells are present at low levels in humans; however, the function of these cells is not known. In this study, we demonstrate a rapid expansion of CD25(+)FOXP3(+)CD8(+) regulatory T cells (Tregs) in the blood and multiple tissues following a pathogenic SIV infection in rhesus macaques. The expansion was pronounced in lymphoid and colorectal mucosal tissues, preferential sites of virus replication. These CD8 Tregs expressed molecules associated with immune suppressor function such as CTLA-4 and CD39 and suppressed proliferation of SIV-specific T cells in vitro. They also expressed low levels of granzyme B and perforin, suggesting that these cells do not possess killing potential. Expansion of CD8 Tregs correlated directly with acute phase viremia and inversely with the magnitude of antiviral T cell response. Expansion was also observed in HIV-infected humans but not in SIV-infected sooty mangabeys with high viremia, suggesting a direct role for hyperimmune activation and an indirect role for viremia in the induction of these cells. These results suggest an important but previously unappreciated role for CD8 Tregs in suppressing antiviral immunity during immunodeficiency virus infections. These results also suggest that CD8 Tregs expand in pathogenic immunodeficiency virus infections in the nonnatural hosts and that therapeutic strategies that prevent expansion of these cells may enhance control of HIV infection.
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PMID:Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control. 2005 43

The gastrointestinal tract represents a major site for human and simian immunodeficiency virus (HIV and SIV) replication and CD4(+) T-cell depletion. Despite severe depletion of mucosal CD4(+) T cells, FOXP3(+) regulatory CD4(+) T cells (T(reg)) are highly increased in the gut mucosa of chronically HIV-infected individuals and may contribute to HIV pathogenesis, either by their immunosuppressive function or as a significant target cell population for virus production. Little is known about the susceptibility of mucosal T(reg) to viral infection and the longitudinal effect of HIV/SIV infection on T(reg) dynamics. In this study, we determined the level of SIV infection in T(reg) and nonregulatory CD4(+) T cells (non-T(reg)) isolated from the colon of SIV-infected rhesus macaques. The dynamics of mucosal T(reg) and alterations in the mucosal CD4(+) T-cell pool were examined longitudinally. Our findings indicate that mucosal T(reg) were less susceptible to productive SIV infection than non-T(reg) and thus were selectively spared from SIV-mediated cell death. In addition to improved survival, local expansion of T(reg) by SIV-induced proliferation of the mucosal CD4(+) T-cell pool facilitated the accumulation of mucosal T(reg) during the course of infection. High frequency of mucosal T(reg) in chronic SIV infection was strongly related to a reduction of perforin-expressing cells. In conclusion, this study suggests that mucosal T(reg) are less affected by productive SIV infection than non-T(reg) and therefore spared from depletion. Although SIV production is limited in mucosal T(reg), T(reg) accumulation may indirectly contribute to viral persistence by suppressing antiviral immune responses.
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PMID:Gut mucosal FOXP3+ regulatory CD4+ T cells and Nonregulatory CD4+ T cells are differentially affected by simian immunodeficiency virus infection in rhesus macaques. 2007 75


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