Adrenaline-induced mobilization of T cells in HIV-infected patients

Abstract

The present study aimed to investigate lymphocyte mobilization from peripheral cell reservoirs in HIV-infected patients. Nine HIV-infected patients on stable highly active anti-retroviral therapy (HAART), eight treatment-naive HIV-infected patients and eight HIV- controls received a 1-h adrenaline infusion. The adrenaline infusion induced a three-fold increase in the concentration of lymphocytes in all three groups. All HIV-infected patients mobilized significantly higher numbers of CD8+ cells but less CD4+ cells. All subjects mobilized CD45RA+CD62L+ and CD8+CD28+ cells to a lesser extent than CD45RO+CD45RA- and CD8+CD28-cells. Furthermore, high numbers of CD8+CD38+ cells were mobilized only in the HIV-infected patients. It was therefore predominantly T cells with an activated phenotype which were mobilized after adrenaline stimulation. It is concluded that the HIV-associated immune defect induced an impaired ability to mobilize immune-competent cells in response to stress stimuli. Furthermore, the study does not support the idea that CD4+ T cells are trapped in lymph nodes by HIV antigens, because untreated and HAART-treated HIV-infected patients mobilized similar numbers of CD4+ T cells. Finally, no evidence was found for the existence of a HAART-induced non-circulating pool of CD4+ T cells.

Fig. 1

Blood concentrations of CD4⁺ T cell subpopulations (cells/mm³) before, during and after adrenaline infusion. Geographic mean and 95% confidence interval error bars are shown. Untreated (n = 8) and highly active anti-retroviral therapy (HAART)-treated (n = 9) HIV-infected patients and controls (n = 8). (a) CD4⁺ T cells. (b) CD4⁺CD45RA⁺CD62L⁺ (naive) T cells. (c) CD4⁺CD45RO⁺ (memory) T cells. (d) CD4⁺CD45RA⁺CD62L⁻ (revertant) T cells. (e) CD4⁺CD45RA⁺CD45RO⁺ (transient) T cells. ‡, §, * denote significant difference from baseline values, P < 0.05, P < 0.01 and P < 0.001, respectively; †, ¶ denote significant difference between the HIV-infected group and controls, P < 0.05 and P < 0.01, respectively.

Fig. 2

Blood concentrations of CD8⁺ T cell subpopulations (cells/mm³) before, during and after adrenaline infusion. Geographic mean and 95% confidence interval error bars are shown. Untreated (n = 8) and highly active anti-retroviral therapy (HAART)-treated (n = 9) HIV-infected patients and controls (n = 8). (a) CD8⁺ T cells. (b) CD8⁺CD45RA⁺CD62L⁺ (naive) T cells. (c) CD8⁺CD45RO⁺ (memory) T cells. (d) CD8⁺CD45RA⁺CD62L⁻ (revertant) T cells. (e) CD8⁺CD45RA⁺CD45RO⁺ (transient) T cells. ‡, * denote significant difference from baseline values, P < 0.05 and P < 0.001 (‡⁽¹⁾ only in the controls), respectively; †, ¶, ** denote significant differences between the HIV-infected group and the controls, P < 0.05, P < 0.01 and P < 0.001, respectively.

Fig. 3

Blood concentrations of CD8⁺ T cell subpopulations co-expressing CD28 or CD38 (cells/mm³) before, during and after adrenaline infusion. Geographic mean and 95% confidence interval error bars are shown. Untreated (n = 8) and highly active anti-retroviral therapy (HAART)-treated (n = 9) HIV-infected patients and controls (n = 8). (a) CD8⁺CD28⁺ T cells. (b) CD8⁺CD38⁺ T cells. (c) CD8⁺CD28⁻ T cells. (d) CD8⁺CD38⁻ T cells. ‡, §, * denote significant differences from baseline values, P < 0.05, P < 0.01 and P < 0.001 (‡⁽²⁾ and §⁽²⁾, only in the HIV-infected group), respectively; †, ¶ denote group effect between the HIV-infected group and the controls, P < 0.05 and P < 0.01, respectively.