Congenital deficiency of CD4⁺ T lymphocytes is associated with the progressive loss of CD8⁺ T cells

Combined Immunodeficiency due to the selective absence of CD4+ T lymphocytes is a rare form of immunodeficiency disease characterized by low CD4+ T cell number at birth, decreased production of IL-2, elevated CD8+ T cell numbers, poor mitogen induced lymphocyte proliferation, and dysgammaglobulinemia. We evaluated an eleven year old male child with congenital CD4+ T cell lymphopenia from birth in order to define the regulatory role CD4+ T cells play in immune development. The child, who showed no evidence of HIV infection, received therapy with IVIG and TMP/SMZ prophylaxis since age 6 months. While his growth and development have been normal, medical problems have included reactive airway disease, mucocutaneous candidiasis, recurrent bacterial sinusitis, and Mycobacterium avium pneumonia. Blood CD4+ T cell number was low at birth and has remained low throughout life (243 +/- 143 cells/ul). Blood CD8+ T cell number, which was elevated for the first year of life, fell to low numbers by age two and has progressively been depleted over time (125 +/- 86 cells/ul). Mitogen response to PHA has been 12% of controls. IgA and IgM, while present, have been low throughout life (IgA 86 +/- 35 mg/dl and IgM 35 +/- 7 mg/dl), This immune disorder is characterized by opportunistic infections similar to those observed in HIV infection. However, normal growth and development is preserved. The progressive loss of CD8+ T cells may be a result of an attrition mechanism impacting both CD4+ and CD8+ T cell number. Alternatively CD8+ T cell number may depend on the presence of CD4+ T cells. This novel immunodeficiency disease may serve as a human model for the immunopathogenesis of HIV infection.

Duke Scholars

Author John William Sleasman Pediatrics, Allergy and Immunology