In vivo imaging of mucosal CD4+ T cells using single photon emission computed tomography in a murine model of colitis.
Immune responses that occur in the context of human infectious and inflammatory diseases are usually studied by sampling cells from peripheral blood, from biopsies, or by end-point harvests at necropsy. These approaches are likely to yield information that is incomplete and/or non-representative. Here, we report the development and validation of a non-invasive method to localize and to quantitate the disposition of specific subpopulations of cells in vivo. In a murine model of dextran sulfate sodium (DSS)-induced colitis, CD4+ T cells were visualized in the colon by single photon emission computed tomography (SPECT-CT) after injection of monoclonal, non-depleting, indium-111 (111In) labeled anti-CD4+ antibodies. The SPECT-CT colon uptake ratio (CUR) was found to correlate (p<0.01) with the number of total CD4+ T cells and with standard measures of pathology (colon length, cell counts, and histopathologic evidence of apoptosis, edema, and cellular infiltrates) as assessed by direct examination of diseased colon. Each of these parameters, including the SPECT-CT signal uptake, increased as a function of DSS dose (p<0.05). We conclude that CT-SPECT imaging using an 111In-labeled anti-CD4+ antibody is reflective of traditional parameters of pathology in this experimental model of murine colitis. This approach should be readily applicable to the imaging of discrete cell subpopulations in non-human primates and in humans, thus augmenting our understanding of infectious diseases and inflammation in vivo.
Kanwar
Bittoo
B
Department of Medicine, Division of Experimental Medicine, The University of California, San Francisco, San Francisco, CA 94143-1234, USA.
Gao
Dong Wei
DW
Hwang
Andrew B
AB
Grenert
James P
JP
Williams
Simon P
SP
Franc
Benjamin
B
McCune
Joseph M
JM
D000818:Animals; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000000981:diagnostic imaging* / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007205:Indium Radioisotopes; D007413:Intestinal Mucosa / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D016264:Dextran Sulfate