The characteristic feature of HIV and some SIV infections is the chronic immune activation that probably drives the continuous CD4 T cell depletion and progression towards AIDS. What exactly causes this aberrant activation is not clear; however, traits inherent to the immune response seem to be more responsible than the virus itself. For example, there are data showing that the same strain of virus (SIV) can induce lasting but non-pathogenic infection in one primate species (sooty mangabeys) and devastating disease which resembles AIDS in the other (rhesus macaques). It may be therefore instructive to study details of immune response against SIV in pathogenic conditions. B lymphocytes are not spared from overall activation during HIV/SIV infection – in fact, sick individuals display hypergammaglobulinemia, or elevated levels of IgG antibodies. Switched antibodies are generally produced by cells that derive from the germinal center reaction where B lymphocytes interact with the unique subset of CD4 T cells called follicular helpers (TFH). Follicular helpers can be distinguished from other CD4 T cell subsets by their expression of CXCR5, ICOS, PD-1 and the transcription factor Bcl-6 as well as the high level of IL-21 cytokine secretion. TFH have been shown to be crucial for the successful generation of plasma cell and memory compartments. The recent paper takes a look at germinal centers during SIV infection in monkeys that develop AIDS-like disease.
Authors use immunohistological staining and flow cytometry to prove that PD-1 positive CD4 T cells (according to what we know TFH population) accumulate in germinal centers along disease progression in rhesus macaques infected with SIVmac239. They also correlate the enhanced PD-1 expression on CD4 T cells with remodeling of B cell populations that reside in lymph nodes (the trend is towards reducing naïve subset and enriching memory subsets) and the increased IgG secretion. Additionally, it is demonstrated that CD8 T cells are excluded from germinal centers (both in naïve and infected monkeys). Investigators conclude that the buildup of TFH population during pathogenic SIV infection may play the important role in shifting B cell activation status. Apart from that they suggest that germinal centers could form anatomical sites of potential viral escape due to the lack of CD8 T cells presence (and alleged insufficient control of infected CD4 T cells there).
The experimental setting of this publication is restricted to recording several immune parameters at time points that represent either acute or chronic SIV infection. However, it is interesting because it attempts the systematic documentation of changes in the immune response that may underlie the pathologic immune activation distinctive for some primate lentiviruses. The obvious question for the future is whether there may be any significant changes in germinal center reaction between species that develop pathogenic or non-pathogenic SIV infection.
Hong, J., Amancha, P., Rogers, K., Ansari, A., & Villinger, F. (2012). Spatial Alterations between CD4+ T Follicular Helper, B, and CD8+ T Cells during Simian Immunodeficiency Virus Infection: T/B Cell Homeostasis, Activation, and Potential Mechanism for Viral Escape The Journal of Immunology, 188 (7), 3247-3256 DOI: 10.4049/jimmunol.1103138