This result is consistent with HLA-Cw*0602 playing a part directly in the pathogenesis of guttate psoriasis.

Highly active anti-retroviral therapy (HAART) is associated with reduction in the morbidity and mortality of patients with advanced HIV-1 disease. The ability of such treatment to improve immune responses against HIV-1 and opportunistic pathogens is variable and limited. Addition of cytokine immunotherapy to this treatment may improve immune responses. IL-2 with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to HIV-1+ individuals receiving HAART with undetectable viral loads, and CD4 counts < 100 cells/microl. In one patient presenting with Mycobacterium avium complex (MAC) infection, we evaluated the effect of cytokine immunotherapy on lymphocyte phenotype; plasma viral load; proliferative responses to mitogens, recall and HIV-1 antigens; cytokine production and message in response to non-specific and specific stimuli; and natural killer (NK) cell activity. Proliferation assays were performed in two similar patients. Before cytokine immunotherapy the predominant CD8+ population was mainly CD28-. No proliferation or IL-2 production was seen in response to mitogens, recall or HIV-1 antigens; and no HIV-1 peptide-specific interferon-gamma (IFN-gamma)-secreting cells were present. Low levels of IL-4 were detected in response to antigens to which patients had been exposed, associated with up-regulated expression of costimulatory molecules influenced by IL-4. Following IL-2 administration, loss of IL-4 was associated with increased NK cell activity and HIV-1 peptide-specific and non-specific IFN-gamma-producing cells. Proliferative responses associated with IL-2 production and responsiveness were only seen after subsequent concomitant administration of GM-CSF with IL-2. These changes mirrored clinical improvement. An imbalance of lymphocyte subsets may account for immune unresponsiveness when receiving HAART. Restoration of responses following immunotherapy suggests a shift towards a lymphocyte profile with anti-pathogen activity.

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The aetiopathogenesis of psoriasis is unknown, but genetic and environmental factors may be involved. Psoriasis may not be one disease but a cutaneous inflammatory reaction pattern consequent upon several different independent or related stimuli in susceptible individuals. There are controversial issues regarding the immunological basis of psoriasis and the role of CD4 vs. CD8 T lymphocytes. Psoriasis has been associated with HLA-Cw6 and Cw7 by serology and specifically with HLA-Cw*0602 by polymerase chain reaction (PCR) typing. Psoriasis is probably no more common in HIV infection than in the general population; however, it may appear for the first time or pre-existing psoriasis may worsen and be difficult to treat in HIV disease. We have investigated the prevalence of HLA-C alleles, in the specific clinical context of HIV infection complicated by type 1 psoriasis, in a case control study of 14 men with HIV disease and type 1 psoriasis and 147 HIV-infected patients without psoriasis. Typing was performed using PCR with sequence-specific amplification primers. Eleven of 14 patients (79%) with psoriasis carried the HLA-Cw*0602 allele compared with 24.5% of those without psoriasis (odds ratio = 11.31; 95% confidence limits 2. 73 to 65.36; P = 0.0001). Two patients without the HLA-Cw*0602 allele carried instead the closely related Cw*0401/3 allele. The results confirm the previously reported association between the HLA-Cw*0602 allele and type 1 psoriasis, and suggest that the association with HLA-Cw*0602 is stronger in HIV-associated psoriasis although this trend needs to be supported by a larger sample. The immunodysregulation resulting from HIV infection may trigger psoriasis in those genetically predisposed by the Cw*0602 allele. As CD8 T cells recognize antigens in the context of class I major histocompatibility complex, the identification of an HLA class I association in HIV-associated psoriasis strengthens the argument for an important role for CD8 + T lymphocytes in the immunopathogenesis of psoriasis. Investigations of the pathogenesis of psoriasis should take account of clinical and other subtypes already identified.

The aim of the study was to determine whether the expression of CD38 on CD8 T cells can identify patients with virological failure on antiretroviral therapy (ART). DesignThis was a cross-sectional study of patients attending a single HIV clinic in London. MethodsThe expression of CD38 on CD8 T cells was assessed using a biologically calibrated flow cytometry protocol. Patients were characterized by lymphocyte subset and viral load measurements. Characteristics including historical CD4 T cell counts, therapeutic history, co-infections and demographics were obtained from medical records. Results Elevated levels of CD8 CD38high T cells were found in HIV-1-infected patients who failed to suppress viral replication with ART; however, this parameter lacked sufficient sensitivity and specificity to replace viral load testing in assessing the efficacy of ART. Increased levels of CD8 CD38 high cells were associated with reduced CD4 T cell counts in HIV-1-infected patients on ART after correcting for known determinants of CD4 T-cell recovery. ConclusionsThe expression of CD38 on CD8 T cells lacks sufficient sensitivity and specificity to be used as a surrogate marker for viral load to monitor HIV-1 infection. T-cell activation is associated with reduced CD4 T-cell reconstitution in patients receiving ART.Keywords: antiretroviral therapy, CD38, HIV-1, immune activation IntroductionActivation of T lymphocytes is a characteristic feature of untreated HIV-1 infection [1][2][3][4][5][6]. Attempts to use activation profiles of lymphocytes in the monitoring of antiretroviral (ARV)-treated patients have suggested a role for measuring CD8 T-cell activation [7][8][9][10]. T-cell activation can be defined in several ways. Cell surface markers (CD25, CD38, CD69 and HLA-DR) and serum markers (neopterin, b2 microglobulin, soluble CD8 and soluble CD25) have all been used to define T-cell activation in HIV-1 infection [11][12][13][14][15][16]. The most established marker of immune activation in HIV-1 infection is the expression of CD38 on CD8 T cells. Studies have shown the expression of CD38 on CD8 T cells to be independent of CD4 T-cell counts and HIV-1 RNA viral load as a marker of disease progression in HIV-1 infection [17][18][19][20][21]. Antiretroviral therapy (ART) results in decreased T-cell activation, including diminished expression of CD38 on CD8 T cells. There is conflicting evidence regarding levels of T-cell activation and the degree of CD4 T-cell recovery after effective ART, with some evidence supporting a role of immune activation limiting CD4 T-cell recovery [14], while other studies have shown no effect [22]. 18,19,[23][24][25]. In healthy adults, monocytes (but very few CD8 T cells) express high levels of CD38, whereas granulocytes and some naïve (CD45RA) CD8 T cells express low or intermediate levels of CD38. Therefore, a CD38 side-scatter dot plot in healthy controls can be used to select the monocyte population as a positive control for CD8 T cells that strongly express CD38 (CD8 CD38 high T cells) [24].Routine ...