Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection - PubMed (original) (raw)

Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection

Timothy W Schacker et al. Clin Vaccine Immunol. 2006 May.

Abstract

The organized structure of lymphatic tissues (LTs) constitutes a microenvironment referred to as a niche that plays a critical role in immune system homeostasis by promoting cellular interactions and providing access to cytokines and growth factors on which cells are dependent for survival, proliferation, and differentiation. In chronic human immunodeficiency virus type 1 (HIV-1) infection, immune activation and inflammation result in collagen deposition and disruption of this LT niche. We have previously shown that these fibrotic changes correlate with a reduction in the size of the total population of CD4+ T cells. We now show that this reduction is most substantial within the naïve CD4+ T-cell population and is in proportion to the extent of LT collagen deposition in HIV-1 infection. Thus, the previously documented depletion of naïve CD4+ T cells in LTs in HIV-1 infection may be a consequence not only of a decreased supply of thymic emigrants or chronic immune activation but also of the decreased ability of those cells to survive in a scarred LT niche. We speculate that LT collagen deposition might therefore limit repopulation of naïve CD4+ T cells with highly active antiretroviral therapy, and thus, additional treatments directed to limiting or reversing inflammatory damage to the LT niche could potentially improve immune reconstitution.

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Figures

FIG. 1.

FIG. 1.

Comparison of CD4+ area to actual count. The percent area that stains with diaminobenzidine (i.e., CD4+ T cells) is compared to the number of cells manually counted in the image. A total of 117 images (the 1st, 10th, and 18th images from each subject in the analysis) were hand counted using MetaMorph (Trenton, NJ) analysis, where each cell is identified by placing a small hash mark over it with the mouse and the computer tallies the number of hash marks. In panel A, 156 cells were counted. Using Photoshop and the image analysis tools, the percent area CD4+ was found to be 31% (B). Panel C shows the correlation between all images from the 32 patients (P < 0.0001, r = 0.73) and can be described by the following equation: number of CD4+ T cells = (−61.06389 + 11.76418) × % CD4+ area.

FIG. 2.

FIG. 2.

Example of collagen deposition in inguinal lymph node tissue from two patients, one without HIV infection (A) and one with HIV infection and AIDS (B). In panel A, there is minimal deposition of collagen that is found mostly around high endothelial venules (black arrow), as expected. In panel B, there is significant deposition of collagen that is increased around the high endothelial venules (black arrow) and is also found throughout the T-cell zone (red arrow).

FIG. 3.

FIG. 3.

T-cell zone fibrosis is correlated with the size of the LT naïve and effector memory population. The sizes of the naïve (A), overall memory (B), effector memory (C), and central memory (D) CD4+ T-cell populations are compared to the amount of TZ fibrosis. There is a negative and significant correlation between the size of the naïve CD4+ T-cell population and TZ fibrosis (_r_2 = −0.55, P = 0.0008); however, there is no correlation between the size of the memory CD4+ T cells and TZ fibrosis (_r_2 = 0.35). However, when we compared the sizes of the effector and central memory subpopulations, we found a positive and significant correlation between the effector memory cells and TZ fibrosis (_r_2 = 0.59, P = 0.0003) and no correlation with central memory cells (_r_2 = 0.16).

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