CD3+CD56+ and CD3-CD56+ lymphocytes in the cerebrospinal fluid of persons with HIV-1 subtypes B and C

Abstract

The transactivator of transcription (Tat) is a HIV regulatory protein which promotes viral replication and chemotaxis. HIV-1 shows extensive genetic diversity, HIV-1 subtype C being the most dominant subtype in the world. Our hypothesis is the frequency of CSF CD3⁺CD56⁺ and CD3^-CD56^dim is reduced in HIV-1C compared to HIV-1B due to the Tat C30S31 substitution in HIV-1C. 34 CSF and paired blood samples (PWH, n = 20; PWoH, n = 14) were studied. In PWH, the percentage of CD3⁺CD56⁺ was higher in CSF than in blood (p < 0.001), comparable in both compartments in PWoH (p = 0.20). The proportion of CD3^-CD56^dim in CSF in PWH was higher than PWoH (p = 0.008). There was no subtype differences. These results showed CNS compartmentalization of NKT cell response in PWH.

Keywords: Flow cytometry; HIV-1C; Human immunodeficiency virus (HIV); Immunophenotyping; Natural killer (NK) cells; T lymphocytes with natural killer activity (NKT).

Fig. 1.

Proportion of CD3⁺CD56⁺ and CD3⁻ CD56^dim lymphocytes in gated CD45 in CSF (black) and peripheral blood (blue) by HIV serostatus and HIV-1 subtype. From a) to d), the box plots represent the medians and interquartile ranges, whiskers represent the maximum and minimum values, and dots represent individuals. The red dashed lines indicate mean ± two standard deviation in the HIV negative control group. a) CD3⁺CD56⁺ and b) CD3⁻ CD56^dim were compared between PWH and PWoH, HIV-1 subtypes B and C, and plasma and CSF. *p = 0.060 after multiple testing correction using Benjamini Hochberg method. c) CD3⁺CD56⁺ and d) CD3⁻ CD56^dim were compared between the groups categorized according to the HIV RNA in CSF and peripheral blood compartments. *p = 0.11 after adjusting for multiple comparisons with Tukey’s HSD test. e) the frequency of CSF samples CD3⁻ CD56^dim (black) and CD3⁺CD56⁺ (gray) lymphocytes between the groups categorized according with the HIV RNA in CSF and blood compartments. Ctrl, HIV negative control group. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 1.

Proportion of CD3⁺CD56⁺ and CD3⁻ CD56^dim lymphocytes in gated CD45 in CSF (black) and peripheral blood (blue) by HIV serostatus and HIV-1 subtype. From a) to d), the box plots represent the medians and interquartile ranges, whiskers represent the maximum and minimum values, and dots represent individuals. The red dashed lines indicate mean ± two standard deviation in the HIV negative control group. a) CD3⁺CD56⁺ and b) CD3⁻ CD56^dim were compared between PWH and PWoH, HIV-1 subtypes B and C, and plasma and CSF. *p = 0.060 after multiple testing correction using Benjamini Hochberg method. c) CD3⁺CD56⁺ and d) CD3⁻ CD56^dim were compared between the groups categorized according to the HIV RNA in CSF and peripheral blood compartments. *p = 0.11 after adjusting for multiple comparisons with Tukey’s HSD test. e) the frequency of CSF samples CD3⁻ CD56^dim (black) and CD3⁺CD56⁺ (gray) lymphocytes between the groups categorized according with the HIV RNA in CSF and blood compartments. Ctrl, HIV negative control group. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 1.

Proportion of CD3⁺CD56⁺ and CD3⁻ CD56^dim lymphocytes in gated CD45 in CSF (black) and peripheral blood (blue) by HIV serostatus and HIV-1 subtype. From a) to d), the box plots represent the medians and interquartile ranges, whiskers represent the maximum and minimum values, and dots represent individuals. The red dashed lines indicate mean ± two standard deviation in the HIV negative control group. a) CD3⁺CD56⁺ and b) CD3⁻ CD56^dim were compared between PWH and PWoH, HIV-1 subtypes B and C, and plasma and CSF. *p = 0.060 after multiple testing correction using Benjamini Hochberg method. c) CD3⁺CD56⁺ and d) CD3⁻ CD56^dim were compared between the groups categorized according to the HIV RNA in CSF and peripheral blood compartments. *p = 0.11 after adjusting for multiple comparisons with Tukey’s HSD test. e) the frequency of CSF samples CD3⁻ CD56^dim (black) and CD3⁺CD56⁺ (gray) lymphocytes between the groups categorized according with the HIV RNA in CSF and blood compartments. Ctrl, HIV negative control group. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2.

Scatterplots of correlations between biomarkers in CSF and PB. Correlation coefficients (ρ, 95% confidence intervals) estimated using Spearman’s rank-order method.