T-cell subsets in health, infectious disease, and idiopathic CD4+ T lymphocytopenia
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Published on: April 16, 2015
1Department of Medicine, Cornell University Medical College, New York, NY 10021.
Insights
Understanding normal CD4+ and CD8+ T-cell counts is crucial for diagnosing immune deficiencies. Low CD4 counts, especially with a declining trend and low CD4:CD8 ratio, warrant investigation for HIV and other immune suppressive conditions.
Area of Science:
- Immunology
- Infectious Diseases
- Hematology
Background:
- Normal absolute values for CD4+ and CD8+ T-lymphocyte subsets are essential for assessing immune status.
- Infectious diseases significantly influence T-lymphocyte subset values.
- Idiopathic CD4+ T lymphocytopenia and severe unexplained HIV-negative immune suppression (ICL/SUHIS) represent newly identified syndromes.
Purpose of the Study:
- To update knowledge on normal absolute values for CD4+ and CD8+ peripheral T-lymphocyte subsets.
- To elucidate how infectious diseases affect these T-lymphocyte values.
- To discuss these findings in the context of ICL/SUHIS.
Main Methods:
- Literature search of studies published after 1978 (introduction of monoclonal antibody T-lymphocyte subset analysis).
- Inclusion of English-language articles with patient numbers, selection criteria, and absolute T-cell subset counts (means, ranges, standard deviations).
- Data sourced from MEDLARS computer search and personal files.
Main Results:
- Bacterial, viral, parasitic, and fungal infections, along with analytic variance and biologic factors, impact T-lymphocyte subsets.
- Advanced HIV infection is characterized by CD4 counts <400/mm3, progressive CD4 depletion, and a CD4:CD8 ratio <1.0.
- The definition of ICL/SUHIS based solely on CD4 count may lead to misdiagnosis in diverse conditions, including physiologic CD4 lymphopenia.
Conclusions:
- Individuals with CD4 counts <300-400/mm3, progressive CD4 decline, and CD4:CD8 ratio <1.0 require thorough investigation for HIV and other immune deficiencies.
- Investigating potential novel infectious causes is most promising in patients with CD4 counts below normal levels, particularly those with syndromes like ICL/SUHIS.
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.
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