Abstract
CMV colitis has been reported in immunocompromized patients with severe deficiency of CD4+ T cells and T cell functions. In this study we present an extensive immunological analysis in a patient with primary hypogammaglobulinemia and CMV colitis who had normal numbers of CD3+T, CD4+T and CD8+T cells, and normal T cell proliferative responses to mitogens and recall antigens. Naïve (TN), central (TCM), and effector (TEM) memory subsets of CD4+ and CD8+ T cells, Granzyme+ and Perforin+ CD8+ T cells, PD-1+ T cells, CD4 Treg, CD8 Treg, and CMV tetramer specific CD8+ T cells were analyzed with specific antibodies and isotype controls using multicolor flow cytometry. CD8 TEM, Granzyme+ and Perforin+, and PD-1 CD8+T cells were increased, whereas CD8 TN and CD8 TCM cells were decreased in the patient as compared to controls. CMV tetramer+ CD8+ T cells were decreased in the patient. These data demonstrate that a deficiency of CMV-specific CD8+ T cells even in the presence of normal CD4+ T cell numbers and normal T cell functions may predispose patients with primary hypogammaglobulinemia to CMV colitis.
Highlights
Cytomegalovirus (CMV) is a double stranded DNA virus of the herpes virus family, which can lead to a spectrum of clinical presentations, from latent infection to disseminated disease
To best of our knowledge, the first detailed immunological analysis in a patient with primary hypogammaglobulinemia and CMV colitis, who has normal numbers of CD3+, CD4+, and CD8+ T cell subsets, and normal responses to mitogens and soluble antigens
Antibodies and Reagents CD4 PerCP, CD8 PerCP, CD45RA APC, CCR7FITC, CD183 PE, Foxp3 PE, CD170a PE, Granzyme-B FITC, Perforin FITC, and PD-1 APC antibodies were purchased from BD Parmingen (San Jose, California). iTAg MHC tetramer HLA-A∗0201 and CMV PP65 Tetramer PE were obtained from MBL International corps (Woburn MA)
Summary
Cytomegalovirus (CMV) is a double stranded DNA virus of the herpes virus family, which can lead to a spectrum of clinical presentations, from latent infection to disseminated disease. Rare gastrointestinal infections with CMV have been described in patients with common variable immunodeficiency [6,7,8,9,10,11,12,13,14,15] These patients had low CD4+ T cells, and in none of these studies detailed immunological analyses, including CMV-specific CD8+ T cells were reported. To best of our knowledge, the first detailed immunological analysis in a patient with primary hypogammaglobulinemia and CMV colitis, who has normal numbers of CD3+, CD4+, and CD8+ T cell subsets, and normal responses to mitogens and soluble antigens. A computed tomography scan of the abdomen and pelvis with contrast revealed diffuse small bowel mucosal hyperenhancement consistent with enteritis, with no evidence of free air or recurrent bowel perforation He underwent EGD and colonoscopy with no complications.
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