Both cellular and humoral immunity are important for the controlling HIV infection. However, little data is known about immune cells in different compartments in very early acute HIV infection (AHI). The RV254 Thai study captures participants in AHI from prior to viral load (VL) peak (Fiebig 1 and 2), at peak VL (Fiebig 3) and during VL decay (Fiebig 4/5).
Frozen matched peripheral blood mononuclear cells (PBMC) and lymph node (LN) cells of 29 acute HIV-infected Thais (wk.0), 29 antiretroviral therapy (ART)-treated, chronically infected and uninfected Thais (n=13) were studied. The immune cells of CD4, CD8 and B cells were characterized by flow cytometry.
Frequencies of resting memory (RM) B cells (CD21+CD27+IgG+CD20+) were significantly decreased whereas frequencies of tissue-like memory (TLM) B cells (CD21-CD27-IgG+CD20+) were significantly increased during AHI in PBMC but not in LN. However, frequencies of RM and TLM B cells were not restored as the same level in healthy donors after ART. Frequencies of plasmablast (IgD-CD38hiCD20+) B cells were evaluated in PBMC at all AHI stages but not in LN. Importantly, in LN, frequencies of CD4 Tfh cells (CXCR3-PD1+CXCR5+CD45RA-CD4+) were not elevated compared to controls and significantly lower than in chronic infection except for a transient increase at Fiebig 2 (Fig.1a), suggesting that CD4 Tfh cells are depleted or not generated in AHI after Fiebig 2 impacting B cell maturation. Germinal Center (GC) B cells (CD38++IgD-) showed a similar transient increase in Fiebig 2 in LN that did not persist in later AHI stages (Fig.1b) suggesting that GC formation is impaired in AHI. Interestingly, frequencies of CD4 Tfh cells were associated with frequencies of GC B cells (p=0.0009) (Fig.1c). Moreover, both CD4 and CD8 T cell subsets showed activated effector (Ki67+Bcl-2lo) cells as early as Fiebig 1 in PBMC and Fiebig 2 in LN followed by an increase in later stages of AHI in both compartments. Interestingly, frequencies of effector CD4 and CD8 T cells and HIV-specific CD8 T cells correlated between PBMC and LN. In contrast, other immune subsets exhibited decreasing frequencies in blood during AHI while remaining stable in LN.
The phenotypes of immune cells are unique in blood vs. LN. Understanding the immune cells alteration in these compartments during AHI may help defining the mechanisms leading to lack of immune control in natural HIV infection.