Purpose: To update our knowledge about normal absolute values for CD4+ and CD8+ peripheral T-lymphocyte subsets and to show how these values are influenced by infectious disease. These data are discussed in the context of a newly identified syndrome, idiopathic CD4+ T lymphocytopenia and severe unexplained human immunodeficiency virus (HIV)-negative immune suppression (ICL/SUHIS).
Data identification: Studies done after 1978, when T-lymphocyte subset analysis using monoclonal antibodies was introduced, identified from a MEDLARS computer search and from personal files.
Study selection: All English-language articles that included the number of patients studied; the criteria for patient selection; and the means, ranges, and standard deviations for absolute counts of peripheral T-cell subsets.
Results of data analysis: The effects of certain bacterial, viral, parasitic, and fungal infections; analytic variance; and biologic factors on T-lymphocyte subsets must be considered in assessing such values in health and disease. Quantitative T-cell abnormalities secondary to advanced HIV infection may be dissociated from physiologic changes, congenital disorders, and most other conditions by documentation of absolute CD4 counts of less than 400/mm3, a progressive depletion of CD4 cells, and a CD4:CD8 ratio of less than 1.0. Designation of ICL/SUHIS as a new syndrome, dependent solely on CD4 cell count, raises the possibility that persons with an extraordinary diversity of conditions, including those with stable, "physiologic" CD4 lymphopenia, will be given the diagnosis.
Conclusions: Persons with a CD4 count of less than 300 to 400/mm3, a progressive decline in absolute CD4 count, and a CD4:CD8 ratio of less than 1.0 should be aggressively investigated for HIV infection as well as for other causes of immune deficiency, regardless of intercurrent infections. The search for potential novel infectious causes in syndromes such as ICL/SUHIS may be most productive among such a subset of all persons with CD4 counts less than normal levels.