Co-infection by human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1): does immune activation lead to a faster progression to AIDS?

Abstract

Background: Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1.

Methods: We enrolled 29 patients co-infected by HTLV-1 and HIV (co-infected), 59 patients mono-infected by HIV (HIV) and 16 healthy controls (HC), respectively.For phenotypic analysis, cells were stained with the following fluorochrome-labeled anti-human monoclonal antibodies CD4-APC, CD8-PerCP, CD25-PE, CD62L-FITC, CD45RA-FITC. CD45RO-PE, CD38-PE; being analysed by four-colour flow cytometry.

Results: We initially found that CD4+ T cell counts were significantly higher in co-infected, as compared to HIV groups. Moreover, CD4+ T Lymphocytes from co-infected patients presented significantly higher levels of CD45RO and CD25, but lower levels of CD45RA and CD62L, strongly indicating that CD4+ T cells are more activated under HTLV-1 plus HIV co-infection.

Conclusion: Our data indicate that HTLV-1/HIV co-infected patients progress with higher CD4+ T cell counts and higher levels of activation markers. In this context, it is conceivable that in co-infected individuals, these higher levels of activation may account for a faster progression to AIDS.

Figure 1

Absolute CD4+ T cell counts in different HIV clinical stages, among different HTLV status. There is a consistent and stable high absolute CD4 T cell count in co-infected individuals, contrasting with the progressive decrease of this cell subset in the monoinfected group, related to the progression of HIV disease. p value for Anova trend test was 0.000 and 0.945 for HIV/HTLV-1 and HIV groups respectively.

Figure 2

Distribution of T cell subsets in HIV/HTLV-1 co-infected, HIV mono-infected and healthy Mozambican subjects. Co-infected patients presented higher CD4+CD45RO+ (memory cells, C), CD8+CD38+ (activated cells, E) and lower CD4+CD45RA+ (naïve cells, A) and CD4+CD62L+ (naïve cells, H). *p < 0.05, as ascertained by One Way Anova. HIV/HTLV = coinfected, HIV = mono-infected by HIV and HC = healthy controls.

Figure 3

Activated and naïve T cell profiles HIV/HTLV-1 co-infected, HIV mono-infected and healthy Mozambican subjects. Dot plots show the typical phenotype of activated (upper panels) and naïve T lymphocytes (lower panel). Upper panels reveal that co-infected patients presented with higher density of CD38 molecules on T CD8+ T cells. Co-infected patients presented lower frequency of CD4⁺CD62L⁺ cells when compared with HIV positive patients and health controls (lower panel).

Figure 4

Changes in the subsets of T cells in the distinct HIV clinical stages. CD8+CD45RO+ (D) remained unchanged in the various HIV clinical stages in both groups. CD38+ on CD4+ and CD8+ T cells (E and F), CD4+CD25+ and CD4+CD45RO+ subsets were increased from clinical stage I through III in both groups. CD4+CD45RA+ (A), CD8+CD45RA+ (B) and CD4+CD62L+ (H) decreased from stage I through III. Co-infected patients in the clinical stage III for CD4+CD25+ and CD4+CD45RO+ and CD4+CD45RA+ did not follow the pattern observed in HIV mono-infected individuals. I = HIV Clinical Stage I, II = HIV Clinical Stage I, III = HIV Clinical Stage III.

Figure 5

Correlation between naïve CD4 (CD4⁺CD45RA⁺) or activated CD8 (CD8⁺CD38⁺) T lymphocytes with HIV-1 viral Load. Panels A and B depict a negative correlation between CD4+CD45RA+ (naive cells) and HIV-1 viral load in both co-infected and HIV-1 subjects. By contrast, lower panels show a positive correlation between CD8+ CD38 (activated cells, C and D) and HIV-1 viral load in both co-infected and HIV-1 subjects.